North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: position on standards of care and areas of need.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC's inaugural meetings are presented herein.

Plasmonic Diamond Membranes for Ultrafast Silicon Vacancy Emission.

Silicon vacancy centers (SiVs) in diamond have emerged as a promising platform for quantum sciences due to their excellent photostability, minimal spectral diffusion, and substantial zero-phonon line emission. However, enhancing their slow nanosecond excited-state lifetime by coupling to optical cavities remains an outstanding challenge, as current demonstrations are limited to ∼10-fold. Here, we couple negatively charged SiVs to sub-diffraction-limited plasmonic cavities and achieve an instrument-limited ≤8 ps lifetime, corresponding to a 135-fold spontaneous emission rate enhancement and a 19-fold photoluminescence enhancement. Nanoparticles are printed on ultrathin diamond membranes on gold films which create arrays of plasmonic nanogap cavities with ultrasmall volumes. SiVs implanted at 5 and 10 nm depths are examined to elucidate surface effects on their lifetime and brightness. The interplay between cavity, implantation depth, and ultrathin diamond membranes provides insights into generating ultrafast, bright SiV emission for next-generation diamond devices.

Advances in non-clear cell renal cell carcinoma management: From heterogeneous biology to treatment options.

Non-clear cell renal cell carcinoma (nccRCC) makes up nearly one quarter of all RCC subtypes, commonly impacts younger patients, and is often metastatic at presentation. Compared to clear-cell RCC (ccRCC), nccRCC typically has a worse prognosis in the metastatic setting, with overall survival durations that are ~10 months shorter. The nccRCC consists of a wide range of different histological subtypes, the majority of which are composed of papillary, chromophobe, renal medullary carcinoma, translocation RCC, collecting duct carcinoma and unclassified RCC. Most clinical trials have either excluded or only included small numbers of patients with nccRCC; owing to the lack of prospective studies focusing on this population, data on response rates and survival outcomes are lacking. NccRCC treatment is a nascent field with various therapeutic modalities and combinations under investigation, often based on data extrapolated from therapeutic studies in ccRCC. We herein review the use and outcomes of cytotoxic chemotherapy, various combination modalities of tyrosine kinase inhibitors and immune checkpoint inhibitors, and targeted agents. We discuss active ongoing clinical trials for patients with nccRCC and future directions in the treatment of this rare disease. Historically, treatment for nccRCC has been adopted from the standard of care for patients with ccRCC, although these treatments are less effective in the nccRCC population. As we begin to understand the underlying biology of these tumors, clinical trials have been able to slowly accrue and include more patients with various subtypes of nccRCC. There remains much room for improvement in this area of need, but there is hope on the horizon.

Ultrathin Pyroelectric Photodetector with Integrated Polarization-Sensing Metasurface.

An abundance of metallic metasurfaces have been realized with miniscule, intricate features capable of tailored scattering, reflection, and absorption; however, high losses through heat limit their use in optoelectronics. Here, codesign of a detector and a polarization-sensing metasurface overcomes this challenge by utilizing the heat generation for integrated pyroelectric detection of the incoming light polarization. Using a nanogap metasurface with asymmetric metallic elements, polarization-sensitive photodetection exhibits high extinction ratios up to 19 for orthogonally polarized light and allows extraction of Stokes parameters with <12% deviation from theoretical values. This polarization-sensitive photodetector is ultrathin, consisting of active layers of only 290 nm, and exhibits fast response times of ∼2 ns. The structure is fully integrated, requiring no external cameras, detectors, or power sources, and points toward the creation of layered, multifunctional devices that utilize exotic metasurface properties for novel and compact sensing and imaging.

Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: A Single Center Experience.

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially. METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models. RESULTS: We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0). CONCLUSION: Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. BPDCN cells characteristically express several markers on their cell surfaces including CD123, CD4, and CD56. Because of its rarity and challenging clinical presentation, there was no standard of care in managing BPDCN for decades and its prognosis overall was poor. However, as understanding of this rare neoplasm has increased, so have treatment options. The conventional cytotoxic chemotherapy regimens once used in the treatment of BPDCN were modest in their impact on disease relapse until paired with hematopoietic stem cell transplant. Although recent data suggest that there still remains a role for chemotherapeutic agents, targeted modalities have expanded the overall BPDCN treatment landscape. The CD123-targeted agent, tagraxofusp, was the first Food and Drug Administration-approved monotherapy in the treatment of BPDCN. Since its inception, several CD123-targeted and other cell-surface agents have been investigated, with many agents still in the preclinical stages. Although relapsed/refractory disease and central nervous system disease both remain formidable areas of research, there are several promising therapeutic approaches that could have a significant impact on the trajectory of treatment. This review will provide detailed insight on the novel drugs currently in use and those being explored in the management of BPDCN.

Outcomes of patients with intermediate-risk or poor-risk metastatic renal cell carcinoma who received their first cycle of nivolumab and ipilimumab in the hospital because of symptomatic disease: The MD Anderson Cancer Center experience.

Nivolumab plus ipilimumab (nivo/ipi) is an approved therapy for patients with intermediate-risk or poor-risk metastatic renal cell carcinoma (mRCC). Clinical factors that guide the selection of this regimen for patients with mRCC are urgently needed. We retrospectively analyzed medical records of patients with mRCC who were hospitalized at MD Anderson Cancer Center because of cancer-related symptoms and received their first cycle of nivo/ipi in the inpatient setting. Clinical parameters, including demographics, histology, clinical history, response, and survival, were collected. The 4-month survival probability, progression-free survival (PFS), and overall survival (OS) were calculated using Kaplan-Meier methods. Between November 2017 and 21 June 2020 patients were identified that fit the search: 19 patients (91%) had poor-risk disease based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score; 17 patients (81%) had ≥4 risk factors; and 9 patients (43%) had sarcomatoid features on histology. Shortness of breath (28%) and abdominal pain (19%) were the two most common reasons for hospitalization. Partial response was achieved in 14% (3/21) of patients. Median PFS for all patients was 1.7 months (95% CI 0-3.9); median OS for all patients was 1.7 months (95% CI 0-4.2); and the 4-month survival probability was 36% (95% CI 25%-47%). In this retrospective study, patients with intermediate-risk or poor-risk mRCC who are hospitalized at a large tertiary referral center for cancer-related symptoms derive limited clinical benefit from nivo/ipi when started in the inpatient setting. Alternative, more effective systemic therapies should be considered for these patients.

Household air pollution, ultrasound measurement, fetal biometric parameters and intrauterine growth restriction.

BACKGROUND: Low birthweight, intrauterine growth restriction (IUGR) and perinatal mortality have been associated with air pollution. However, intervention studies that use ultrasound measurements to assess the effects of household air pollution (HAP) on fetal biometric parameters (FBP) are rare. We investigated the effect of a cookstove intervention on FBP and IUGR in a randomized controlled trial (RCT) cohort of HAP-exposed pregnant Nigerian women. METHODS: We recruited 324 women early in the second trimester of pregnancy. Between 16 and 18 weeks, we randomized them to either continue cooking with firewood/kerosene (control group) or receive a CleanCook stove and ethanol fuel (intervention group). We measured fetal biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and ultrasound-estimated fetal weight (U-EFW) in the second and third trimesters. The women were clinically followed up at six regular time points during their pregnancies. Once during the women's second trimester and once during the third, we made 72-h continuous measurements of their personal exposures to particulate matter having aerodynamic diameter < 2.5 µm (PM2.5). We adopted a modified intent-to-treat approach for the analysis. Differences between the intervention and control groups on impact of HAP on fetal growth trajectories were analyzed using mixed effects regression models. RESULTS: There were no significant differences in fetal growth trajectories between the intervention and control groups. CONCLUSIONS: Larger studies in a setting of low ambient air pollution are required to further investigate the effect of transitioning to a cleaner fuel such as ethanol on intrauterine growth. TRIAL REGISTRATION: ClinicalTrials.gov NCT02394574 ; September 2012.

Practice patterns and clinical outcomes of platelet alloimmunization in a comprehensive cancer center.

BACKGROUND: Platelet transfusion refractoriness (PTR) secondary to human leukocyte antigen (HLA) alloimmunization is a challenge in the treatment of hematology-oncologypatients and increases the risk of morbidity and mortality from bleeding events. Guidelines for treating PTR have not been clearly described in literature. We aim to describe the practice patterns for the management of PTR secondary to HLA alloimmunization, and to assess the mortality, thrombosis and bleeding-related clinical outcomes at 30 days from diagnosis. METHODS: A retrospective review of 51 cases of PTR secondary to HLA alloimmunization were analyzed. RESULTS: The majority of patients (98 %) had a diagnosis of hematological malignancy of which 88.2 % were undergoing active chemotherapy. Clinically relevant bleeding, by ISTH criteria, was observed in 33.3 %; hemorrhagic shock was diagnosed in 7%. The rate of bleeding-related mortality was estimated at 7.8 %. The use of antifibrinolytics and plasma products (including intravenous immunoglobulin) was more common in cases with major versus non-major bleeding. Grade A or B1U HLA matched products were available in less than half of cases. CONCLUSIONS: There is heterogeneity in the management of the bleeding risk and bleeding events during PTR, with antifibrinolytics more commonly used in patients who suffered severe bleeding. Grade A and B1U HLA-matched platelets are not always readily available, and HLA-typing and HLA-antibody testing are not always performed prior to PTR. Prospective randomized control trials may help to determine the safety and efficacy of antifibrinolytics and other supportive measures in the management of PTR.

Predictors of Infectious Complications after Targeted Prophylaxis for Prostate Needle Biopsy.

PURPOSE: The incidence of infectious complications after transrectal ultrasound guided prostate needle biopsy is rising. We sought to identify the incidence and predictors of infection in a large cohort of men undergoing biopsy who receive targeted prophylaxis. MATERIALS AND METHODS: We retrospectively reviewed the records of 5,214 consecutive patients who underwent transrectal ultrasound guided prostate needle biopsy from January 2013 to December 2014 at UroPartners, a large urology group comprising 28 clinics in metropolitan Chicago. At 1 microbiology laboratory all swabs were processed, the presence of fluoroquinolone resistant gram-negative rods was identified and sensitivity tests were performed. Prophylaxis for biopsy was guided by rectal swab culture. Characteristics of patients with and without infectious complications were compared using the Kruskal-Wallis and chi-square tests. Multivariable logistic regression was done to determine predictors of infectious complications. Analyses were performed with R, version 2.14.2 (https://www.r-project.org/). RESULTS: Of the 5,214 biopsies performed 56 infectious (1.1%) and 24 sepsis complications (0.46%) were found. On univariable analysis nonCaucasian race and fluoroquinolone resistant microbes were predictors of infection (p <0.05). On multivariable analysis fluoroquinolone resistant rectal vault flora (OR 9.98, 95% CI 3.79-26.3) and the number of biopsy cores taken (OR 1.28 per core, 95% CI 1.04-1.54) were independent predictors of infection. CONCLUSIONS: Despite targeted prophylaxis patients with fluoroquinolone resistant rectal vault flora have higher odds of infectious complications following transrectal ultrasound guided prostate needle biopsy. In these patients one should consider using other biopsy approaches or techniques to minimize risk.

Randomized Controlled Ethanol Cookstove Intervention and Blood Pressure in Pregnant Nigerian Women.

RATIONALE: Hypertension during pregnancy is a leading cause of maternal mortality. Exposure to household air pollution elevates blood pressure (BP). OBJECTIVES: To investigate the ability of a clean cookstove intervention to lower BP during pregnancy. METHODS: We conducted a randomized controlled trial in Nigeria. Pregnant women cooking with kerosene or firewood were randomly assigned to an ethanol arm (n = 162) or a control arm (n = 162). BP measurements were taken during six antenatal visits. In the primary analysis, we compared ethanol users with control subjects. In subgroup analyses, we compared baseline kerosene users assigned to the intervention with kerosene control subjects and compared baseline firewood users assigned to ethanol with firewood control subjects. MEASUREMENTS AND MAIN RESULTS: The change in diastolic blood pressure (DBP) over time was significantly different between ethanol users and control subjects (P = 0.040); systolic blood pressure (SBP) did not differ (P = 0.86). In subgroup analyses, there was no significant intervention effect for SBP; a significant difference for DBP (P = 0.031) existed among preintervention kerosene users. At the last visit, mean DBP was 2.8 mm Hg higher in control subjects than in ethanol users (3.6 mm Hg greater in control subjects than in ethanol users among preintervention kerosene users), and 6.4% of control subjects were hypertensive (SBP ≥140 and/or DBP ≥90 mm Hg) versus 1.9% of ethanol users (P = 0.051). Among preintervention kerosene users, 8.8% of control subjects were hypertensive compared with 1.8% of ethanol users (P = 0.029). CONCLUSIONS: To our knowledge, this is the first cookstove randomized controlled trial examining prenatal BP. Ethanol cookstoves have potential to reduce DBP and hypertension during pregnancy. Accordingly, clean cooking fuels may reduce adverse health impacts associated with household air pollution. Clinical trial registered with www.clinicaltrials.gov (NCT02394574).

Thioarsenate Toxicity and Tolerance in the Model System Arabidopsis thaliana.

Thioarsenates form from arsenite under sulfate-reducing conditions, e.g., in rice paddy soils, and are structural analogues of arsenate. Even though rice is one of the most important sources of human arsenic intake, nothing is published about uptake, toxicity, or tolerance of thioarsenates in plants. Experiments using the model system Arabidopsis thaliana showed that monothioarsenate is less toxic than arsenite, but more toxic than arsenate at concentrations ≥25 µM As, reflected in stronger seedling growth inhibition on agar plates. Despite higher toxicity, total As accumulation in roots was lower upon exposure to monothioarsenate compared to arsenate, and a higher root efflux was confirmed. Root-shoot translocation was higher for monothioarsenate than for arsenate. Compared to the wild type (Col-0), both arsenate and monothioarsenate induced higher toxicity in phytochelatin (PC)-deficient mutants (cad1-3) as well as in glutathione biosynthesis (cad2) and PC transport (abcc12) mutants, demonstrating the important role of the PC pathway, not only for arsenate, but also for monothioarsenate detoxification. In Col-0, monothioarsenate induced relatively higher accumulation of PCs than arsenate. The observed differences in plant uptake, toxicity, and tolerance of thioarsenate vs oxyarsenate show that studying the effects of As on plants should include experiments with thiolated As species.

Glaciation as a destructive and constructive control on mountain building.

Theoretical analysis predicts that enhanced erosion related to late Cenozoic global cooling can act as a first-order influence on the internal dynamics of mountain building, leading to a reduction in orogen width and height. The strongest response is predicted in orogens dominated by highly efficient alpine glacial erosion, producing a characteristic pattern of enhanced erosion on the windward flank of the orogen and maximum elevation controlled by glacier equilibrium line altitude, where long-term glacier mass gain equals mass loss. However, acquiring definitive field evidence of an active tectonic response to global climate cooling has been elusive. Here we present an extensive new low-temperature thermochronologic data set from the Patagonian Andes, a high-latitude active orogen with a well-documented late Cenozoic tectonic, climatic and glacial history. Data from 38° S to 49° S record a marked acceleration in erosion 7 to 5 Myr ago coeval with the onset of major Patagonian glaciation and retreat of deformation from the easternmost thrust front. The highest rates and magnitudes of erosion are restricted to the glacial equilibrium line altitude on the windward western flank of the orogen, as predicted in models of glaciated critical taper orogens where erosion rate is a function of ice sliding velocity. In contrast, towards higher latitudes (49° S to 56° S) a transition to older bedrock cooling ages signifies much reduced late Cenozoic erosion despite dominantly glacial conditions here since the latest Miocene. The increased height of the orogenic divide at these latitudes (well above the equilibrium line altitude) leads us to conclude that the southernmost Patagonian Andes represent the first recognized example of regional glacial protection of an active orogen from erosion, leading to constructive growth in orogen height and width.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic): clinical review in a rapidly emerging field.

VEXAS syndrome is a recently described entity characterized by systemic inflammatory and hematologic manifestations. The disease was first characterized by Beck et al. in 2020 in a study characterizing 25 patients with undiagnosed adult-onset inflammatory syndromes. While the literature regarding VEXAS syndrome has grown exponentially since 2020, there is still much to be understood. This lack of information leads to challenges in both the diagnosis and treatment of patients with VEXAS syndrome. Patients will often have a variety of clinical symptoms that can lead to missed or delayed diagnoses. Additionally, awareness of VEXAS syndrome is still developing among clinicians. In this comprehensive review, we summarize the current literature regarding VEXAS syndrome, and explore clinical updates of this emerging disease state. Our aim of this review is to increase awareness regarding this new disease state and identify research areas to better understand future treatment approaches for patients with VEXAS syndrome.

Plating Versus Intramedullary Nailing of OTA/AO 43C1 and C2 Intra-articular Distal Tibia Fractures: A Propensity Score and Multivariate Analysis.

OBJECTIVE: To compare rates of reduction loss, nonunion, and infection in intra-articular distal tibia fractures (IADTF) treated with limited open reduction internal fixation and intramedullary nailing (IMN) as compared to open reduction internal fixation with plate and screws (plate fixation [PF]). DESIGN: Retrospective review. SETTING: Level-I academic trauma center. PATIENT SELECTION CRITERIA: Patients age ≥ 18 with OTA/AO 43C1 and C2 IADTF treated with IMN or PF between 2013-2021. OUTCOME MEASURES AND COMPARISONS: Loss of reduction, surgical site infection (SSI), nonunion, and patient-reported outcomes (PROs) were compared for IMN versus PF treatments. RESULTS: One hundred ten patients met the inclusion criteria (IMN 33 and PF 77). There was no loss of reduction found. Seventeen nonunions (15% overall; IMN 4/33 and PF 13/77) and 13 SSIs (12% overall; IMN 2/33 and PF11/77) were identified. Despite several risk factors being identified for nonunion and SSI in bivariate analysis, only open fracture remained significant as a risk factor for both nonunion (odds ratio 0.09 for closed fracture, 95% confidence interval, 0.02-0.56, P = 0.009) and SSI (odds ratio 0.07 for closed fracture, 95% confidence interval, 0.06-0.26, P = 0.012) in the multivariate model. Propensity scoring based on presurgical variables was significantly different between patients who received IMN versus PF ( P = 0.03); however, logistic regression incorporating the propensity score revealed no significant association with nonunion and SSI. Adjusting for the propensity score, there remained no association comparing IMN versus PF with nonunion and SSI ( P = 0.54 and P = 0.17, respectively). There was also no difference in PROs between IMN and PF (physical function: P = 0.25 and pain interference: P = 0.21). CONCLUSIONS: Overall nonunion and SSI prevalence was 15% and 12%, respectively, in operatively treated OTA/AO 43C1 and C2 IADTF. An open fracture was a significant risk factor for nonunion and SSI. Metaphyseal fixation through IMN or PF did not affect loss of reduction, nonunion, SSI, or PROs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Durable Objective Response to Lurbinectedin in Small Cell Bladder Cancer with TP53 Mutation: A Molecular-Directed Strategy.

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring TP53 mutations and amplifications in E2F3 and MYC family complexes.

Long-Term Clinical, Radiological, and Mortality Outcomes Following Pneumonitis in Nonsmall Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Analysis.

AIMS: Despite known short-term mortality risk of immune checkpoint inhibitor (ICI) pneumonitis, its impact on 1-year mortality, long-term pulmonary function, symptom persistence, and radiological resolution remains unclear. METHODS: We retrospectively analyzed 71 nonsmall cell lung cancer (NSCLC) patients treated with anti-PD(L)1 monoclonal antibodies between 2018-2021, who developed pneumonitis. Clinical and demographic covariates were collected from electronic medical record. Cox regression assessed associations with mortality, while logistic regression evaluated associations with persistent symptoms, hypoxemia, and radiological resolution. RESULTS: Steroid-refractory pneumonitis (hazard ratio [HR] = 15.1, 95% confidence interval [95% CI]:3.9-57.8, P < .0001) was associated with higher 1-year mortality compared to steroid-responsive cases. However, steroid-resistant (odds ratio [OR] = 1.4, 95% CI: 0.4-5.1, P = .58) and steroid-dependent (OR = 0.4, 95% CI: 0.1-1.2, P = .08) pneumonitis were not. Nonadenocarcinoma histology (OR = 6.7, 95% CI: 1.6-46.6, P = .01), grade 3+ pneumonitis (OR = 4.6, 95% CI: 1.3-22.7, P = .03), and partial radiological resolution (OR = 6.3, 95% CI: 1.8-23.8, P = .004) were linked to increased pulmonary symptoms after pneumonitis resolution. Grade 3+ pneumonitis (OR = 8.1, 95% CI: 2.3-31.5, P = .001) and partial radiological resolution (OR = 5.45, 95% CI: 1.29-37.7, P = .03) associated with residual hypoxemia. Nonadenocarcinoma histology (OR = 3.6, 95% CI: 1.01-17.6, P = .06) and pretreatment ILAs (OR = 4.8, 95% CI: 1.14-33.09, P = .05) were associated with partial radiological resolution. CONCLUSIONS: Steroid refractory pneumonitis increases 1-year mortality in NSCLC patients. Pretreatment ILAs may signal predisposition to fibrosis-related outcomes, seen as partial resolution, which in turn is associated with postresolution symptoms and residual hypoxemia. These findings offer insights for identifying patients at risk of adverse outcomes post-pneumonitis resolution.

Stranger Things: New Roles and Opportunities for Androgen Receptor in Oncology Beyond Prostate Cancer.

The androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data implicate key roles for AR in additional cancer types, thereby expanding the importance of this drug target beyond prostate cancer. In this mini-review, new roles for AR in other cancer types are discussed as well as their potential for treatment with AR-targeted agents. Our understanding of these additional functions for AR in oncology expand this receptor's potential as a therapeutic target and will help guide the development of new treatment approaches.