Expanding Liver Transplant Opportunities in Older Patients With Nonconventional Grafts.

INTRODUCTION: Broader use of donation after circulatory death (DCD) and nonconventional grafts for liver transplant helps reduce disparities in organ availability. Limited data, however, exists on outcomes specific to nonconventional graft utilization in older patients. As such, this study aimed to investigate outcomes specific to conventional and nonconventional graft utilization in recipients > 70 y of age. METHODS: 1-to-3 matching based on recipient sex, Model for End-Stage Liver Disease score, and donor type was performed on patients ≥70 and <70 y of age who underwent liver transplant alone at Mayo Clinic Arizona between 2015 and 2020. Primary outcomes were posttransplant patient and liver allograft survival for recipients greater than or less than 70 y of age. Secondary outcomes included grafts utilization patterns, hospital length of stay, need for reoperation, biliary complications and disposition at time of hospital discharge. RESULTS: In this cohort, 36.1% of grafts came from DCD donors, 17.4% were postcross clamp offers, and 20.8% were nationally allocated. Median recipient ages were 59 and 71 y (P < 0.01). Recipients had similar Intensive care unit (P = 0.82) and hospital (P = 0.14) lengths of stay, and there were no differences in patient (P = 0.68) or graft (P = 0.38) survival. When comparing donation after brain death and DCD grafts in those >70 y, there were no differences in patient (P = 0.89) or graft (P = 0.71) survival. CONCLUSIONS: Excellent outcomes can be achieved in older recipients, even with use of nonconventional grafts. Expanded use of nonconventional grafts can help facilitate transplant opportunities in older patients.

Donation after circulatory death transplant outcomes using livers recovered by local surgeons.

Donation after circulatory death (DCD) liver transplantation (LT) outcomes have been attributed to multiple variables, including procurement surgeon recovery techniques. Outcomes of 196 DCD LTs at Mayo Clinic Arizona were analyzed based on graft recovery by a surgeon from our center (transplant procurement team [TPT]) versus a local procurement surgeon (non-TPT [NTPT]). A standard recovery technique was used for all TPT livers. The recovery technique used by the NTPT was left to the discretion of that surgeon. A total of 129 (65.8%) grafts were recovered by our TPT, 67 (34.2%) by the NTPT. Recipient age (p = 0.43), Model for End-Stage Liver Disease score (median 17 vs. 18; p = 0.22), and donor warm ischemia time (median 21.0 vs. 21.5; p = 0.86) were similar between the TPT and NTPT groups. NTPT livers had longer cold ischemia times (6.5 vs. 5.0 median hours; p < 0.001). Early allograft dysfunction (80.6% vs. 76.1%; p = 0.42) and primary nonfunction (0.8% vs. 0.0%; p = 0.47) were similar. Ischemic cholangiopathy (IC) treated with endoscopy occurred in 18.6% and 11.9% of TPT and NTPT grafts (p = 0.23). At last follow-up, approximately half of those requiring endoscopy were undergoing a stent-free trial (58.3% TPT; 50.0% NTPT; p = 0.68). IC requiring re-LT in the first year occurred in 0.8% (n = 1) of TPT and 3.0% (n = 2) of NTPT grafts (p = 0.23). There were no differences in patient (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.76-5.03; p = 0.23) or graft (HR, 1.99; 95% CI, 0.98-4.09; p = 0.10) survival rates. Graft survival at 1 year was 91.5% for TPT grafts and 95.5% for NTPT grafts. Excellent outcomes can be achieved using NTPT for the recovery of DCD livers. There may be an opportunity to expand the use of DCD livers in the United States by increasing the use of NTPT.

Outcomes of dual kidney transplants from high KDPI kidneys are superior compared to single kidney high KDPI transplants at 1 year.

Dual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P = .02) and donors had a higher KDPI score (median 96% vs. 91%, P < .0001). DKT operative time was higher compared to SKT (+1.4 hours, P < .0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P = .77) and hospital length of stay (median 4.0 vs. 3.0 days, P = .21) between DKT and SKT. Grade I Clavien-Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P = .008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P = .04), interstitial fibrosis (P = .02), tubular atrophy (P = .01), and arterial thickening (P = .03) on 1-year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1- (P = .004) and 2-years post-transplant (P = .01). There were no differences in patient (HR 1.3, 95% CI .5-3.3, P = .58) or graft (HR 1.1, 95% CI .5-2.3, P = .83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard.

Association of DGF and Early Readmissions on Outcomes Following Kidney Transplantation.

Concerns regarding outcomes and early resource utilization are potential deterrents to broader use of kidneys at risk for delayed graft function (DGF). We assessed outcomes specific to kidneys with DGF that required early readmission following transplant. Three groups were identified: 1) recipients with DGF not requiring readmission, 2) recipients with DGF having an isolated readmission, and 3) recipients with DGF requiring ≥2 readmissions. Most recipients either required a single readmission (26.8%, n = 247) or no readmission (56.1%, n = 517); 17.1% (n = 158), had ≥2 readmissions. Recipients requiring ≥2 readmissions were likely to be diabetic (53.8%, p = 0.04) and have longer dialysis vintage (p = 0.01). Duration of DGF was longer with increasing number of readmissions (p < 0.001). There were no differences in patient survival for those with DGF and 0, 1 and ≥2 readmissions (p = 0.13). Graft survival, however, was lower for those with ≥2 readmissions (p < 0.0001). This remained true when accounting for death-censored graft loss (p = 0.0012). Additional subgroup analysis was performed on mate kidneys with and without DGF and mate kidneys, both with DGF, with and without readmissions. For these subgroups, there were no differences in patient or graft survival. As a whole, patients with DGF have excellent outcomes, however, patients with DGF requiring ≥2 readmissions have lower graft survival. A better understanding of recipient variables contributing to multiple readmissions may allow for improvements in the utilization of DGF at-risk kidneys.

A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.

Transplant outcomes using kidneys from high KDPI acute kidney injury donors.

Kidney transplant (KT) outcomes from high kidney donor profile index (KDPI ≥85%) donors with acute kidney injury (AKI) remain underreported. KT from 172 high KDPI Acute Kidney Injury Network (AKIN) stage 0-1 donors and 76 high KDPI AKIN stage 2-3 donors from a single center were retrospectively assessed. The AKIN 2-3 cohort had more delayed graft function (71% vs. 37%, p < .001). At one year, there were no differences in the estimated glomerular filtration rate (44 ± 17 vs. 46 ± 18, p = .42) or fibrosis on protocol biopsy (ci, p = .85). Donor terminal creatinine (p = .59) and length of delayed graft function (p = .39) did not impact one-year eGFR. There were more primary nonfunction (PNF) events in the high KDPI AKIN 2-3 group (5.3% vs. 0.6%, p = .02). With a median follow-up of 3.8 years, one-year death-censored graft failure was 3.5% for AKIN 0-1 and 14.5% for AKIN 2-3 (HR 2.40, 95% CI 1.24-4.63, p = .01). Although AKIN stage 2-3 high KDPI kidneys had comparable one-year eGFR to AKIN stage 0-1 high KDPI kidneys, there were more PNF occurrences and one-year death-censored graft survival was reduced. Given these findings, additional precautions should be undertaken when assessing and utilizing kidneys from severe AKI high KDPI donors.

Early technical pancreas failure in Simultaneous Pancreas-Kidney Recipients does not impact renal allograft outcomes.

Early pancreas loss in simultaneous pancreas-kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n = 218). Early pancreas allograft loss occurred in 12.8% (n = 28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p = 0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p = 0.22), surgical wound complications (p = 0.12), or rejection episodes occurring in the first year (p = 0.87). Despite differences in DGF, both groups had excellent renal function at 1 year post-transplant (eGFR 64.1 ± 20.8 vs. 65.8 ± 22.9, p = 0.75). There were no differences in patient (HR 0.58, 95% CI 0.18-1.87, p = 0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23-3.06, p = 0.77). One- and 2-year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2 years (p = 0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.

Physician Disruptive Behavior Compromising Safe Care Delivery.

The negative impact and management of disruptive behavior are discussed in the article by Monika Kumar, et al.

Twin Pregnancy Complicated by Gestational Diabetes Mellitus: Maternal and Neonatal Outcomes.

Context: The risk of gestational diabetes mellitus (GDM) in twin pregnancies is more than double that of singleton pregnancies. Although twin pregnancies present unique challenges for fetal growth and prenatal management, the approach to GDM diagnosis and treatment is the same regardless of plurality. Data on pregnancy outcomes for individuals with GDM and a twin pregnancy are limited and conflicting. Objective: To describe the maternal characteristics associated with GDM in twin pregnancies and to assess the associated pregnancy outcomes compared to twin pregnancies unaffected by GDM. Methods: A retrospective cohort study was conducted at Mayo Clinic, Rochester, Minnesota, USA, and included predominantly Causasian women aged 18 to 45 years who received prenatal care for a twin pregnancy from 2017-2022. Maternal characteristics and a broad spectrum of pregnancy outcomes were evaluated. Universal GDM screening involved a 50 g oral glucose challenge test +/- a 100 g oral glucose tolerance test. Results: GDM was diagnosed in 23% pregnancies (n = 104/452). Compared to those without, women with GDM had known risk factors including a higher prepregnancy body mass index (31.1vs 26.3 kg/m2; P < .01) and a prior history of GDM (21.7 vs 5.9%; P < .01). There were no differences in maternal pregnancy complications or neonatal outcomes between groups. Attendance at postpartum glucose testing among women with GDM was poor at 27.9% (29/104). Conclusion: These data suggest that women with twin pregnancies share a similar GDM risk profile to those with singleton pregnancies and provide reassuring evidence that current management for GDM twin pregnancies produces similar outcomes to twin pregnancies without GDM.

Targeting EMT using low-dose Teniposide by downregulating ZEB2-driven activation of RNA polymerase I in breast cancer.

Metastatic dissemination from the primary tumor is a complex process that requires crosstalk between tumor cells and the surrounding milieu and involves the interplay between numerous cellular-signaling programs. Epithelial-mesenchymal transition (EMT) remains at the forefront of orchestrating a shift in numerous cellular programs, such as stemness, drug resistance, and apoptosis that allow for successful metastasis. Till date, there is limited success in therapeutically targeting EMT. Utilizing a high throughput screen of FDA-approved compounds, we uncovered a novel role of the topoisomerase inhibitor, Teniposide, in reversing EMT. Here, we demonstrate Teniposide as a potent modulator of the EMT program, specifically through an IRF7-NMI mediated response. Furthermore, Teniposide significantly reduces the expression of the key EMT transcriptional regulator, Zinc Finger E-Box Binding Homeobox 2 (ZEB2). ZEB2 downregulation by Teniposide inhibited RNA polymerase I (Pol I) activity and rRNA biogenesis. Importantly, Teniposide treatment markedly reduced pulmonary colonization of breast cancer cells. We have uncovered a novel role of Teniposide, which when used at a very low concentration, mitigates mesenchymal-like invasive phenotype. Overall, its ability to target EMT and rRNA biogenesis makes Teniposide a viable candidate to be repurposed as a therapeutic option to restrict breast cancer metastases.

A multi-centric, single-blinded, randomized, parallel-group study to evaluate the effectiveness of nasoalveolar moulding treatment in non-syndromic patients with complete unilateral cleft lip, alveolus and palate (NAMUC study): a study protocol for a randomized controlled trial.

BACKGROUND: Cleft lip and palate (CLP) are among the most common congenital anomaly that affects up to 33,000 newborns in India every year. Nasoalveolar moulding (NAM) is a non-surgical treatment performed between 0 and 6 months of age to reduce the cleft and improve nasal aesthetics prior to lip surgery. The NAM treatment has been a controversial treatment option with 51% of the cleft teams in Europe, 37% of teams in the USA and 25 of cleft teams in India adopting this methodology. This treatment adds to the already existing high burden of care for these patients. Furthermore, the supporting evidence for this technique is limited with no high-quality long-term clinical trials available on the effectiveness of this treatment. METHOD: The NAMUC study is an investigator-initiated, multi-centre, single-blinded randomized controlled trial with a parallel group design. The study will compare the effectiveness of NAM treatment provided prior to lip surgery against the no-treatment control group in 274 patients with non-syndromic unilateral complete cleft lip and palate. The primary endpoint of the trial is the nasolabial aesthetics measured using the Asher McDade index at 5 years of age. The secondary outcomes include dentofacial development, speech, hearing, cost-effectiveness, quality of life, patient perception, feeding and intangible benefits. Randomization will be carried out via central online system and stratified based on cleft width, birth weight and clinical trial site. DISCUSSION: We expect the results from this study on the effectiveness of treatment with NAM appliance in the long term along with the cost-effectiveness evaluation can eliminate the dilemma and differences in clinical care across the globe. TRIAL REGISTRATION: ClinicalTrials.gov CTRI/2022/11/047426 (Clinical Trials Registry India). Registered on 18 November 2022. The first patient was recruited on 11 December 2022. CTR India does not pick up on Google search with just the trial number. The following steps have to be carried out to pick up. How to search: ( https://ctri.nic.in/Clinicaltrials/advsearch.php -use the search boxes by entering the following details: Interventional trial > November 2022 > NAMUC).

Deciphering the effect of maternal postpartum antibiotic prophylaxis on the infant gut microbiome: a whole metagenomic analysis.

Aim: To analyze the impact of postpartum antibiotic (Ab) prophylaxis on the infant gut microbiome. Materials & methods: Whole metagenomic analysis was performed on breast milk and infant fecal samples collected from mother-infant pairs who belonged to two groups: an Ab group comprising mothers who had received a single course of Abs in the immediate postpartum period and a non-Ab group comprising mothers who had not received Abs. Results: The characteristic presence of Citrobacter werkmanii, an emerging multidrug-resistant uropathogen, and a higher relative abundance of genes encoding resistance to specific Abs were noted in samples from the Ab group compared with those from the non-Ab group. Conclusion: Policies regarding prophylactic Ab prescription across government and private health sectors in the postpartum period need to be strengthened.

We studied the impact of antibiotics (Abs) that were taken by mothers as a preventive measure in the immediate postdelivery period on the bacterial diversity of the infant gut. All mother­infant pairs who participated in the study had undergone 'low-risk', normal delivery and practiced exclusive breastfeeding. Stool samples of the infants and breast milk samples of the corresponding mothers were collected for analysis of the pattern of microbial composition. On analysis, it was found that stool samples of the infants in the Ab group comprised opportunistic pathogens and harbored genes encoding resistance to specific Abs. There was a relatively higher abundance of beneficial bacteria in infant stool samples of the non-Ab group. This study highlights the need to reconsider the existing practice of taking Abs as a preventive measure after normal delivery to maintain health and reduce the spread of antimicrobial resistance in this particular region.

Intracranial nanomedicine-gel with deep brain-penetration for glioblastoma therapy.

Glioblastoma Multiforme (GBM) is one of the challenging tumors to treat as it recurs, almost 100%, even after surgery, radiation, and chemotherapy. In many cases, recurrence happens within 2-3cm depth of the resected tumor margin, indicating the inefficacy of current anti-glioma drugs to penetrate deep into the brain tissue. Here, we report an injectable nanoparticle-gel system, capable of providing deep brain penetration of drug up to 4 cm, releasing in a sustained manner up to >15 days. The system consists of ∼222 nm sized PLGA nanoparticles (NP-222) loaded with an anti-glioma drug, Carmustine (BCNU), and coated with a thick layer of polyethylene glycol (PEG). Upon release of the drug from PLGA core, it will interact with the outer PEG-layer leading to the formation of PEG-BCNU nanocomplexes of size ∼33 nm (BCNU-NC-33), which could penetrate >4 cm deep into the brain tissue compared to the free drug (< 5 mm). In vitro drug release showed sustained release of drug for 15 days by BCNU-NP gel, and enhanced cytotoxicity by BCNU-NC-33 drug-nanocomplexes in glioma cell lines. Ex vivo goat-brain phantom studies showed drug diffusion up to 4 cm in tissue and in vivo brain-diffusion studies showed almost complete coverage within the rat brain (∼1.2 cm), with ∼55% drug retained in the tissue by day-15, compared to only ∼5% for free BCNU. Rat orthotopic glioma studies showed excellent anti-tumor efficacy by BCNU-NP gel compared to free drug, indicating the potential of the gel-system for anti-glioma therapy. In effect, we demonstrate a unique method of sustained release of drug in the brain using larger PLGA nanoparticles acting as a reservoir while deep-penetration of the released drug was achieved by in situ formation of drug-nanocomplexes of size <50 nm which is less than the native pore size of brain tissue (> 100 nm). This method will have a major impact on a challenging field of brain drug delivery.

Preventing Future Harm: Identifying the Drivers of an Unsafe Discharge to Improve Safety on an Inpatient Oncology Service.

Cancer Morbidity, Mortality, and Improvement Rounds is a series of articles intended to explore the unique safety risks experienced by oncology patients through the lens of quality improvement, systems and human factors engineering, and cognitive psychology. For purposes of clarity, each case focuses on a single theme, although, as is true for all medical incidents, there are almost always multiple, overlapping, contributing factors. The quality improvement paradigm used here, which focuses on root cause analyses and opportunities to improve care delivery systems, was previously outlined in this journal.This article describes the care of a young patient with aggressive breast cancer, declining performance status, and multiple hospital admissions who died shortly after being discharged home without essential medications or an adequate plan for follow-up. The patient's death due to her malignancy was unavoidable, but she had inadequate resources before her death, leading to avoidable suffering. This outcome resulted from a series of minor errors attributable to inadequate handoffs, challenges establishing realistic goals of care, and hierarchy within and between medical teams that resulted in major lapses at the time of discharge. We explore these issues and discuss how this case led to the establishment of programs designed to empower health care providers and increase engagement of outpatient oncologists at critical points of patients' disease courses.

Human Trafficking Education: A Pilot Study of Integration into Medical School Curriculum.

OBJECTIVES: Few medical schools incorporate formal education on human trafficking (HT) and sex trafficking (ST) into their curriculum. Our objective was to develop, implement, and evaluate education on HT and ST in the first-year medical student curriculum. METHODS: The curriculum included a standardized patient (SP) experience and lecture. As part of their mandatory sexual health course, students interviewed an SP who presented with red flags for ST and then participated in a discussion led by a physician-facilitator in an observed small group setting. A multiple-choice survey to assess knowledge about HT and ST was developed and administered to students before and after the SP interview. RESULTS: Of the 50 first-year medical students, 29 (58%) participated in the survey. Compared with the students' baseline scores (according to the percentage of correct responses), scores after the educational intervention showed a significant increase in percentage correct on questions related to trafficking definition and scope (elder care, P = .01; landscaping, P = .03); victim identification (P < .001); referral to services (P < .001); legal issues (P = .01); and security (P < .001). On the basis of the feedback, a 2-hour lecture, which was adapted from the American Medical Women's Association-Physicians Against the Trafficking of Humans "Learn to Identify and Fight Trafficking" training, was presented the next year to all first-year medical students as part of their longitudinal clinical skills course and before the SP case. Curriculum objectives included learning trafficking definitions, victim/survivor identification, intersections with health care, the local impact of HT, and available resources. CONCLUSION: This curriculum fulfills course objectives and could be replicated at other institutions. Further evaluation of this pilot curriculum is necessary to evaluate its effectiveness.

Reassessing Geographic, Logistical, and Cold Ischemia Cutoffs in Liver Transplantation.

INTRODUCTION: Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. PROJECT AIM: The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. DESIGN: This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. RESULTS: Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P = .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P = .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P = .001). Early allograft dysfunction was common (54.1% vs 52.5%, P = .75) and did not impact hospital length of stay (median 5 vs 6 days, P = .89). There were no differences in biliary complications (P = .11). There were no differences in patient (P = .88) or graft survival (P = .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. CONCLUSION: Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.

Clinical Outcomes in COVID-19 Patients Treated with Immunotherapy.

Introduction: The full impact of COVID-19 infections on patients with cancer who are actively being treated with chemotherapy or immune checkpoint inhibitors (ICIs) has not been fully defined. Our goal was to track clinical outcomes in this specific patient population. Methods: We performed a retrospective chart review of 121 patients (age > 18 years) at the University of Alabama at Birmingham from January 2020 to December 2021 with an advanced solid malignancy that were eligible to be treated with ICIs or on current therapy within 12 months of their COVID-19 diagnosis. Results: A total of 121 patients were examined in this study, and 61 (50.4%) received immunotherapy treatment within 12 months. One quarter of the patients on ICIs passed away, compared to 13% of the post-chemotherapy cohort. Patients who were vaccinated for COVID-19 had lower mortality compared to unvaccinated patients (X2 = 15.19, p < 0.001), and patients with lower ECOG (0.98) were associated with lower mortality compared to patients with worse functional status (0.98 vs. 1.52; t = 3.20; p < 0.01). Conclusions: COVID-19-related ICI mortality was higher compared to patients receiving chemotherapy. However, ICI cessation or delay is unwarranted as long there has been a risk−benefit assessment undertaken with the patient.

Non-small cell lung cancer in the era of immunotherapy.

Immunotherapy for non-small cell lung cancer (NSCLC) has revolutionized treatment for those with advanced disease, and recent data have emerged providing evidence for its benefits in earlier stages of the disease. Several pivotal clinical trials provide compelling data that adaptive immune cells may be highly effective and possibly even curative for NSCLC. Immune checkpoint inhibitors (ICIs) can unleash highly reactive memory immune responses to tumor antigens with durable effects against advanced or recurrent disease. Despite these encouraging results, many critical questions remain in the field including, for example, how to identify the subsets of NSCLC patients who most benefit from ICI treatment, and how ICI efficacy might be enhanced by utilizing combinations or sequencing of agents. A deeper understanding of biological mechanisms involved in lung cancer offers a unique opportunity to further explore the interaction between the adaptive immune landscape and NSCLC. Given the high incidence of lung cancer in Veterans and many Veterans being treated with immunotherapy for this disease, it is timely to have their adequate representation in future clinical trials. New clinical trials focused on Veterans can assist in exploring ways to mitigate resistant mechanisms as well as to investigate predictive and prognostic biomarkers for response to ICIs and other treatments. This paper will review current data and indications for immunotherapy in NSCLC, introduce new areas of research within immunotherapy, and discuss its applicability to the Veteran population.

Patterns of Failure and Optimal Treatment Paradigm for Large, Inoperable, Node-Negative Non-small Cell Lung Cancer.

OBJECTIVES: The ideal non-operative treatment for patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. To inform optimal treatment paradigms for this cohort, we examined patterns of failure and the impact of radiation therapy (RT) and chemotherapy receipt. MATERIALS AND METHODS: Node-negative NSCLC patients with 5+ cm primary tumors receiving definitive RT at our institution were identified. Sites of initial progression were analyzed. Local progression, regional/distant progression, progression-free survival, and overall survival were analyzed via cumulative incidence function and Kaplan-Meier. Associations between local vs. regional/distant progression with treatment and clinicopathologic variables were assessed via univariable and multivariable competing risks regression. RESULTS AND CONCLUSION: We identified 88 patients for analysis. Among patients with recurrent disease (N = 36), initial patterns of failure analysis showed that isolated distant (27.8%) and isolated regional progression (22.2%) were most common. Distant or regional failure as a component of initial failure was seen in 88.9% of patients who progressed, while isolated local failure was uncommon (11.1%). Univariable and multivariable competing risks regression showed that receipt of SBRT was associated with reduced risk of local progression (HR 0.23, P = .012), and receipt of chemotherapy was associated with reduced risk of regional/distant progression (HR 0.12, P = .040). In conclusion, patients with large, node-negative NSCLC treated with definitive RT are at high risk of regional and distant progression. SBRT correlates with a reduced risk of local failure while chemotherapy is associated with reduced regional/distant progression in this patient population. Ideal treatment may include SBRT when feasible with appropriate systemic therapy.