Neuronal, affective, and sensory correlates of targeted helping behavior in male and female Sprague Dawley rats.

Introduction: Empathic behaviors are driven by the ability to understand the emotional states of others along with the motivation to improve it. Evidence points towards forms of empathy, like targeted helping, in many species including rats. There are several variables that may modulate targeted helping, including sex, sensory modalities, and activity of multiple neural substrates. Methods: Using a model of social contact-independent targeted helping, we first tested whether sex differences exist in helping behavior. Next, we explored sex differences in sensory and affective signaling, including direct visualization and an analysis of ultrasonic vocalizations made between animal pairs. Finally, we examined the neural activity in males and females of multiple regions of interest across time. Here, we aim to examine any behavioral differences in our lab's social contact independent targeted helping task between males and females. Results and Discussion: These findings are the first to intimate that, like other prosocial behaviors, males and females may exhibit similar social-independent targeted helping behavior, but the underlying sensory communication in males and females may differ. In addition, this is the first set of experiments that explore the neural correlates of social-independent targeted helping in both males and females. These results lay the groundwork for future studies to explore the similarities and differences that drive targeted helping in both sexes.

Genetic and subjective sensitivity, relationship dynamics, and psychological distress in couples.

Positive and negative aspects of intimate relationships influence mental health and well-being in couples. According to the environmental sensitivity framework, individuals differ in how strongly they are affected by their environment, with some individuals being more or less sensitive to both negative and positive experiences. The present study examined the longitudinal associations between positive and negative relationship dynamics, including marital satisfaction, positive bonding, and negative communication, and psychological distress as well as the extent to which individual differences in genetic and subjective measures of environmental sensitivity moderated the association between relationship dynamics and psychological distress in a sample of couples in the U.S. Army (n = 238 individuals representing 152 unique couples). Sensitivity was measured by self-report and a polygenic score derived from previous genome-wide association study results. Separate three-level multilevel models were conducted for each relationship dynamic and sensitivity variable. Only for subjective (i.e., self-reported) sensitivity did significant cross-level interactions emerge in predicting psychological distress, whereas no such interactions were found for genetic (i.e., polygenic score) sensitivity. Specifically, lower marital satisfaction and positive bonding were associated with higher psychological distress among subjectively highly sensitive individuals, and higher negative communication was associated with higher psychological distress among subjectively highly sensitive individuals. Findings suggest that both low positive and high negative relationship dynamics may have a greater effect on psychological distress among highly sensitive individuals, which may help to inform tailored intervention to meet the unique needs of couples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Biomarker Inference and the Timing of Next-Generation Sequencing in a Multi-Institutional, Cross-Cancer Clinicogenomic Data Set.

PURPOSE: Observational clinicogenomic data sets, consisting of tumor next-generation sequencing (NGS) data linked to clinical records, are commonly used for cancer research. However, in real-world practice, oncologists frequently request NGS in search of treatment options for progressive cancer. The extent and impact of this dynamic on analysis of clinicogenomic research data are not well understood. METHODS: We analyzed clinicogenomic data for patients with non-small cell lung, colorectal, breast, prostate, pancreatic, or urothelial cancers in the American Association for Cancer Research Biopharmaceutical Consortium cohort. Associations between baseline and time-varying clinical characteristics and time from diagnosis to NGS were measured. To explore the impact of informative cohort entry on biomarker inference, statistical interactions between selected biomarkers and time to NGS with respect to overall survival were calculated. RESULTS: Among 7,182 patients, time from diagnosis to NGS varied significantly by clinical factors, including cancer type, calendar year of sequencing, institution, and age and stage at diagnosis. NGS rates also varied significantly by dynamic clinical status variables; in an adjusted model, compared with patients with stable disease at any given time after diagnosis, patients with progressive disease by imaging or oncologist assessment had higher NGS rates (hazard ratio for NGS, 1.61 [95% CI, 1.45 to 1.78] and 2.32 [95% CI, 2.01 to 2.67], respectively). Statistical interactions between selected biomarkers and time to NGS with respect to survival, potentially indicating biased biomarker inference results, were explored. CONCLUSION: To evaluate the appropriateness of a data set for a particular research question, it is crucial to measure associations between dynamic cancer status and the timing of NGS, as well as to evaluate interactions involving biomarkers of interest and NGS timing with respect to survival outcomes.

Racial/ ethnic disparities in availability of volunteer unrelated donors for allogeneic transplantation.

Despite the global unrelated donor (URD) registry size, the degree to which URD availability is a transplant barrier is not established. We evaluated the availability of 3,843 URDs requested for 455 diverse adult patients (predominantly with acute leukemia). URDs for non-Europeans were more likely to be domestic and had markedly lower Donor Readiness Scores. Of URDs requested for confirmatory HLA-typing (CT) alone (i.e. without simultaneous workup), 1,894/3,529 (54%) were available. Availability of domestic URDs was 45%. Donor Readiness Score was highly predictive of CT availability. Compared with Europeans (n=335), more non-European patients (n=120) had >10 URDs requested and <5 available. Of workup requests (after CT or CT-workup), <70% (604/889, 68%) were available. More non-Europeans had <2 URDs available. URD availability for CT was markedly worse for non-Europeans, with availabilities for African, non-Black Hispanic, and Asian patients of 150/458 (33%), 120/258 (47%) and 119/270 (44%), respectively, with further decrements in URD workup availability. Our data suggest the functional size of the URD pool is much smaller than appreciated, mandating major operational changes for transplant Centers and donor registries. Likelihood of donor availability should have a high priority in donor selection. Considering patient ancestry and URD Donor Readiness Scores, Centers should pursue, and registries permit, simultaneous pursuit of many URDs, and abandon futile searches. Patients should be informed about their likelihood of donor availability and alternative options. Finally, while registries should address high URD attrition and speed procurement, use of all HLA-disparate graft types is needed to facilitate timely transplantation for all.

Genomic Characterization and Clinical Outcomes of Patients with Peritoneal Metastases from the AACR GENIE Biopharma Collaborative Colorectal Cancer Registry.

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11-2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08-2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29-0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment. SIGNIFICANCE: Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.

Diabetes alters neuroeconomically dissociable forms of mental accounting.

Those with diabetes mellitus are at high-risk of developing psychiatric disorders, yet the link between hyperglycemia and alterations in motivated behavior has not been explored in detail. We characterized value-based decision-making behavior of a streptozocin-induced diabetic mouse model on a naturalistic neuroeconomic foraging paradigm called Restaurant Row. Mice made self-paced choices while on a limited time-budget accepting or rejecting reward offers as a function of cost (delays cued by tone-pitch) and subjective value (flavors), tested daily in a closed-economy system across months. We found streptozocin-treated mice disproportionately undervalued less-preferred flavors and inverted their meal-consumption patterns shifted toward a more costly strategy that overprioritized high-value rewards. We discovered these foraging behaviors were driven by impairments in multiple decision-making systems, including the ability to deliberate when engaged in conflict and cache the value of the passage of time in the form of sunk costs. Surprisingly, diabetes-induced changes in behavior depended not only on the type of choice being made but also the salience of reward-scarcity in the environment. These findings suggest complex relationships between glycemic regulation and dissociable valuation algorithms underlying unique cognitive heuristics and sensitivity to opportunity costs can disrupt fundamentally distinct computational processes and could give rise to psychiatric vulnerabilities.

Reduced-Intensity Compared to Nonmyeloablative Conditioning in Patients with Non-Hodgkin Lymphoma Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning are preferred for patients with non-Hodgkin lymphoma (NHL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). Although prior studies have suggested that higher-intensity regimens in RIC-NMA conditioning are associated with inferior outcomes in patients with NHL, the optimal conditioning regimen remains unknown. We performed a retrospective single-center analysis to determine outcomes of adult patients with B cell and T cell NHL who underwent allo-HCT and received either RIC or NMA conditioning between March 2008 and December 2019. RIC regimens included fludarabine-cyclophosphamide-thiotepa-4 Gy-total body irradiation (Flu-Cy-TT-4Gy-TBI), fludarabine-melphalan (Flu-Mel), fludarabine-cyclophosphamide-4 Gy-total body irradiation (Flu-Cy-4Gy-TBI), and fludarabine-busulfan-4 (Flu-Bu-4). The NMA regimen comprised fludarabine-cyclophosphamide-2 Gy-total body irradiation (Flu-Cy-2Gy-TBI). The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), nonrelapse mortality (NRM), and the incidence of acute and chronic graft-versus-host-disease (GVHD). Of 279 transplants recipients (median age, 58 years), 110 received RIC (55% Flu-Mel, 38% Flu-Cy-TT-4Gy-TBI, 6% Flu-Bu-4, 1% Flu-Cy-4Gy-TBI) and 169 received NMA conditioning with Flu-Cy-2Gy-TBI. With a median of 64 months of follow-up post-allo-HCT, there was no significant difference in OS between the NMA and RIC groups (median, not reached [NR] versus 103 months; P = .1), and this was maintained on multivariable analysis. Similarly, after adjustment for all independently significant covariates (age, Karnofsky Performance Status [KPS], Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI], and disease histology), the regression analysis showed no significant difference in PFS with RIC compared to NMA conditioning (hazard ratio [HR] 1.38; 95% confidence interval [CI], .92 to 2.09; P = .24). On univariable analysis, there was no significant difference in NRM between the RIC and NMA arms (100-day estimate, 10.0% versus 1.8%; P = .5). After adjustment for age, ethnicity, KPS, HCT-CI, GVHD prophylaxis, and donor source, RIC conditioning was associated with a significantly higher incidence of NRM compared to NMA conditioning (HR, 2.61; 95% CI, 1.04 to 6.52; P = .039). On multivariable analysis, compared with the NMA arm, the RIC arm had higher rates of grade II-IV (HR, 2.25; 95% CI, 1.31 to 3.86; P = .002) and grade III-IV acute GVHD (HR, 5.62; 95% CI, 2.03 to 15.6; P < .001). The findings of this study suggest that NMA conditioning with Flu-Cy-TBI-2Gy may be considered over more intensive RIC regimens for patients with NHL undergoing allo-HCT.

Substance use typologies among young people experiencing homelessness in seven cities across the United States: A latent class analysis.

BACKGROUND: Substance use and other health-risk risk factors, including mental health, trauma, and sexual-risk behaviors, often co-occur among youth experiencing homelessness (YEH). The present study aimed to identify subgroups of YEH based on polysubstance use and the linkages to sociodemographic and health-risk characteristics. METHODS: From June 2016 to July 2017, 1,426 YEH (aged 18-26 years) were recruited from seven cities (Houston, Los Angeles, Denver, Phoenix, New York City, St. Louis, San Jose). Participants provided information via a self-administered electronic survey on substance use, mental health, trauma, sexual risk behaviors, and sociodemographic characteristics. The majority of YEH identified as Black (37.3%), cisgender (92.8%), and heterosexual (69.2%). On average, YEH were 20.9 years (SD = 2.1). This study employed latent class analysis (LCA) to identify subgroups of YEH according to their substance use. Multinomial logistic regression analyses were conducted to identify sociodemographic and health-risk characteristics associated with class-membership. RESULTS: Four latent classes of YEH substance use were identified: (1) high polysubstance use; (2) moderate stimulant and high marijuana, alcohol, and prescription drug use; (3) high marijuana, alcohol, and prescription drug use; (4) low/moderate marijuana and alcohol use. Multinomial logistic regression models indicated that geographic location, gender, race/ethnicity, mental health, trauma history, and sexual risk behaviors were significant correlates of substance use class membership among YEH. CONCLUSIONS: These findings offer important implications for the prevention and treatment of substance use among YEH. Screening protocols should consider co-occurring risk factors such as traumatic experiences, sexual risk behaviors, and mental health history as indicators of polysubstance use.

Mindfulness Intervention Improves Coping and Perceptions of Children's Behavior among Families with Elevated Risk.

Mindfulness-informed interventions (MIIs) are increasingly common but have not been extensively studied among families with elevated levels of risk (e.g., those involved in child protective services and/or receiving financial assistance). These families often experience high rates of stressors that can impact coping strategies, interpersonal dynamics, and relationships. Given that mindfulness has been shown to promote health and wellbeing, this study used a sample from two pilot randomized controlled trials to test the extent to which a mindfulness-informed intervention improved coping strategies and perceptions of children's behavior among 53 families with elevated risk. A principal components analysis with a direct oblimin rotation revealed that cognitive-emotion coping strategies could be characterized by three factors: positive adaptation, negative adaptation, and positive refocusing. Intention-to-treat analysis indicated significant group by time differences, with intervention participants demonstrating improvements in positive refocusing coping, positive adaptation coping, and perceptions of children's behavior problems compared to participants in the waitlist control group. No significant differences were found for negative adaptation coping strategies. Findings provide preliminary support for the benefits of mindfulness training in a sample generally underrepresented in the mindfulness intervention literature.

Incidental eagle carcass detection can contribute to fatality estimation at operating wind energy facilities.

Risk of birds colliding with wind turbines, especially protected species like bald eagle and golden eagle in the U.S., is a fundamental wildlife challenge the wind industry faces when developing and operating projects. The U.S. Fish and Wildlife Service requires wind energy facilities that obtain eagle take permits document permit compliance through fatality monitoring. If trained Operations and Maintenance (O&M) staff can reliably detect and report carcasses during their normal routines, and their detection probability can be estimated, then their 'incidental detections' could contribute substantially towards demonstrating permit compliance. Our primary objective was to quantify incidental detection of eagle carcasses by O&M staff under a variety of landscape contexts and environmental conditions throughout a single year. We used the incidental detection probabilities, along with raptor carcass persistence data and area adjustments, to calculate overall probability of incidental detection (i.e., incidental g). We used feathered decoys as eagle-carcass surrogates for monthly detection trials at 6 study sites throughout the U.S. We evaluated the primary drivers of incidental detection using logit regression models including season, viewshed complexity, and a derived variable called the "density quartile" as covariates. We used an Evidence of Absence-based approach to estimate the overall probability of incidental detection. The incidental detection probabilities ranged from 0.28 to 0.78 (mean = 0.48). Detection probabilities decreased as viewshed complexity increased and as distance from the turbine increased. The resulting overall probability of incidental detection ranged from 0.07 to 0.47 (mean = 0.31). The primary drivers of variability in incidental g were detection probability and the area adjustment. Results of our research show that O&M staff were effective at detecting trial carcasses incidentally. Incorporating incidental detection in eagle fatality monitoring efforts is a reliable means of improving estimates of a facility's direct impacts on eagles.

Outcomes Following Early Postoperative Adjuvant Radiosurgery for Brain Metastases.

Importance: Adjuvant stereotactic radiosurgery (SRS) enhances the local control of resected brain metastases (BrM). However, the risks of local failure (LF) and potential for posttreatment adverse radiation effects (PTRE) after early postoperative adjuvant SRS have not yet been established. Objective: To evaluate whether adjuvant SRS delivered within a median of 14 days after surgery is associated with improved LF without a concomitant increase in PTRE. Design, Setting, and Participants: This prospective cohort study examines a clinical workflow (RapidRT) that was implemented from 2019 to 2022 to deliver SRS to surgical patients within a median of 14 days, ensuring all patients were treated within 30 days postoperatively. This prospective cohort was compared with a historical cohort (StanRT) of patients with BrM resected between 2013 and 2019 to assess the association of the RapidRT workflow with LF and PTRE. The 2 cohorts were combined to identify optimal SRS timing, with a median follow-up of 3.3 years for survivors. Exposure: Timing of adjuvant SRS (14, 21, and 30 days postoperatively). Main Outcomes and Measures: LF and PTRE, according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria. Results: There were 438 patients (265 [60.5%] female patients; 23 [5.3%] Asian, 27 [6.2%] Black, and 364 [83.1%] White patients) with a mean (SD) age of 62 (13) years; 377 were in the StanRT cohort and 61 in the RapidRT cohort. LF and PTRE rates at 1 year were not significantly different between RapidRT and StanRT cohorts. Timing of SRS was associated with radiographic PTRE. Patients receiving radiation within 14 days had the highest 1-year PTRE rate (18.08%; 95% CI, 8.31%-30.86%), and patients receiving radiation between 22 and 30 days had the lowest 1-year PTRE rate (4.10%; 95% CI, 1.52%-8.73%; P = .03). LF rates were highest for patients receiving radiation more than 30 days from surgery (10.65%; 95% CI, 6.90%-15.32%) but comparable for patients receiving radiation within 14 days, between 15 and 21 days, and between 22 and 30 days (≤14 days: 5.12%; 95% CI, 0.86%-15.60%; 15 to ≤21 days: 3.21%; 95% CI, 0.59%-9.99%; 22 to ≤30 days: 6.58%; 95% CI, 3.06%-11.94%; P = .20). Conclusions and Relevance: In this cohort study of adjuvant SRS timing following surgical resection of BrM, the optimal timing for adjuvant SRS appears to be within 22 to 30 days following surgery. The findings of this study suggest that this timing allows for a balanced approach that minimizes the risks associated with LF and PTRE.

Patterns of CMV infection after letermovir withdrawal in recipients of posttransplant cyclophosphamide-based transplant.

Reactivation of latent cytomegalovirus (CMV) is increased in recipients of allogeneic hematopoietic cell transplantation (allo-HCT) with seropositive CMV using posttransplant cyclophosphamide (PT-Cy)-based graft-versus-host disease (GVHD) prophylaxis. Letermovir, a novel DNA terminase complex inhibitor, reduces the incidence of clinically significant CMV infection (csCMVi) in this population; however, parameters that predict csCMVi after letermovir withdrawal are not well described. Here, we examined clinical and immunological parameters in 294 recipients of PT-Cy-based allo-HCT, including 157 patients with CMV, of whom 80 completed letermovir prophylaxis without csCMVi and subsequently stopped letermovir. In this population, the median duration of letermovir exposure was 203 days (interquartile range [IQR], 160-250 days). After letermovir withdrawal, the 90-day cumulative incidence of csCMVi was 23.0% (95% confidence interval, 14.3-32.8). There were no episodes of CMV end-organ disease. Hypogammaglobulinemia before letermovir discontinuation was predictive of csCMVi (hazard ratio, 0.33; 95% confidence interval, 0.12-0.93; P = .03), whereas T-cell and B-cell reconstitution before letermovir withdrawal were not predictive of csCMVi. Higher numbers of natural killer cells were found before letermovir withdrawal in patients who experienced csCMVi (median, 202 vs 160; P = .03). In recipients with seropositive CMV, CD3+CD4-CD8+ T-cell reconstitution was faster in patients with CMV regardless of letermovir exposure. Taken together, these data suggest that csCMVi after letermovir withdrawal was frequent in patients treated with PT-Cy, despite prolonged exposure. Strategies to boost CMV-specific adaptive immunity in patients with persistent hypogammaglobulinemia is a logical pathway to reduce csCMVi after letermovir withdrawal.

Parallel worlds and mixed economies: multi-proxy analysis reveals complex subsistence systems at the dawn of early farming in the northeast Baltic.

The transition from foraging to farming was a key turning point in ancient socio-economies. Yet, the complexities and regional variations of this transformation are still poorly understood. This multi-proxy study provides a new understanding of the introduction and spread of early farming, challenging the notions of hierarchical economies. The most extensive biological and biomolecular dietary overview, combining zooarchaeological, archaeobotanical, dietary stable isotope and pottery lipid residue analyses is presented, to unravel the nature and extent of early farming in the 3rd millennium cal BCE in the northeast Baltic. Farming was introduced by incoming Corded Ware cultural groups (CWC), but some dietary segregation existed within these communities, with some having more access to domesticates, others incorporating more wild resources into their diet. The CWC groups coexisted in parallel with local hunter-fisher-gatherers (HFG) without any indication of the adoption of domesticates. There was no transition from foraging to farming in the 3rd millennium cal BCE in the NE Baltic. Instead, we see a complex system of parallel worlds with local HFGs continuing forager lifeways, and incoming farmers practising mixed economies, with the continuation of these subsistence strategies for at least a millennium after the first encounter with domesticated animals.

Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal.

International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer. SIGNIFICANCE: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.

The Simplified Comorbidity Index predicts non-relapse mortality in reduced-intensity conditioning allogeneic haematopoietic cell transplantation.

Comorbidity assessment before allogeneic haematopoietic cell transplantation (allo-HCT) is essential for estimating non-relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of 'high-yield' comorbidities and older age. The SCI was predictive of NRM in myeloablative CD34-selected allo-HCT. Here, we evaluated the SCI in a single-centre cohort of 327 patients receiving reduced-intensity conditioning followed by unmanipulated allografts from HLA-matched donors. Among the SCI factors, age above 60, mild renal impairment, moderate pulmonary disease and cardiac disease were most frequent. SCI scores ranged from 0 to 8, with 39%, 20%, 20% and 21% having scores of 0-1, 2, 3 and ≥4 respectively. Corresponding cumulative incidences of 3-year NRM were 11%, 16%, 22% and 27%; p = 0.03. In multivariable models, higher SCI scores were associated with incremental risks of all-cause mortality and NRM. The SCI had an area under the receiver operating characteristic curve of 65.9%, 64.1% and 62.9% for predicting 1-, 2- and 3-year NRM versus 58.4%, 60.4% and 59.3% with the haematopoietic cell transplantation comorbidity index. These results demonstrate for the first time that the SCI is predictive of NRM in patients receiving allo-HCT from HLA-matched donors after reduced-intensity conditioning.

Efficacy of PD-(L)1 blockade monotherapy compared with PD-(L)1 blockade plus chemotherapy in first-line PD-L1-positive advanced lung adenocarcinomas: a cohort study.

BACKGROUND: Single-agent PD-(L)1 blockade (IO) alone or in combination with chemotherapy (Chemotherapy-IO) is approved first-line therapies in patients with advanced lung adenocarcinomas (LUADs) with PD-L1 expression ≥1%. These regimens have not been compared prospectively. The primary objective was to compare first-line efficacies of single-agent IO to Chemotherapy-IO in patients with advanced LUADs. Secondary objectives were to explore if clinical, pathological, and genomic features were associated with differential response to Chemotherapy-IO versus IO. METHODS: This was a multicenter retrospective cohort study. Inclusion criteria were patients with advanced LUADs with tumor PD-L1 ≥1% treated with first-line Chemotherapy-IO or IO. To compare the first-line efficacies of single-agent IO to Chemotherapy-IO, we conducted inverse probability weighted Cox proportional hazards models using estimated propensity scores. RESULTS: The cohort analyzed included 866 patients. Relative to IO, Chemotherapy-IO was associated with improved objective response rate (ORR) (44% vs 35%, p=0.007) and progression-free survival (PFS) in patients with tumor PD-L1≥1% (HR 0.84, 95% CI 0.72 to 0.97, p=0.021) or PD-L1≥50% (ORR 55% vs 38%, p<0.001; PFS HR 0.68, 95% CI 0.53 to 0.87, p=0.002). Using propensity-adjusted analyses, only never-smokers in the PD-L1≥50% subgroup derived a differential survival benefit from Chemotherapy-IO vs IO (p=0.013). Among patients with very high tumor PD-L1 expression (≥90%), there were no differences in outcome between treatment groups. No genomic factors conferred differential survival benefit to Chemotherapy-IO versus IO. CONCLUSIONS: While the addition of chemotherapy to PD-(L)1 blockade increases the probability of initial response, never-smokers with tumor PD-L1≥50% comprise the only population identified that derived an apparent survival benefit with treatment intensification.