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PURPOSE EA1181 (ClinicalTrials.gov identifier: NCT04266249 ) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)–positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point—3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)—will be reported when data mature. METHODS Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER–]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER– and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER– tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER– and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

The NCCN Guidelines for Survivorship offer guidance for health care providers who care for survivors of adult-onset cancer. These guidelines include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from cancer and its treatment and provide a framework for care coordination. They also present guidance for helping cancer survivors to enhance their wellness and maintain a healthy lifestyle. This article summarizes the panel’s current recommendations and recent updates regarding anxiety, depression, distress, and trauma in cancer survivors.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of certain sites within the body. Pleural mesothelioma is the most common type and represents approximately 85% of mesotheliomas. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for evaluation and treatment in patients with pleural mesothelioma. The NCCN Guidelines will continue to be updated annually based on available clinical evidence and panel consensus.

Abstract Background There is limited data on immune checkpoint inhibitor (ICI) use in patients with non-small cell lung cancer (NSCLC) and known pericardial effusions. Methods This international multi-center observational retrospective study included patients with advanced NSCLC with or without pericardial effusions receiving ICIs. Immune-related adverse events (irAEs) were graded per CTCAE v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Cox proportional hazards multivariable models assessed the association between survival outcomes and clinicopathologic variables, and an inverse probability of treatment weighting (IPTW) model compared outcomes between the two groups. Results A total of 1248 patients with advanced NSCLC treated with ICIs across 13 institutions were included. Of these, 85 patients (6.8%) had pre-existing pericardial effusions. Compared to controls, patients with pericardial effusions were younger (median age 63 vs 67 years, P = .007), diagnosed more frequently with PD-L1 positive tumors (96% vs 76%, P < .001), and had a higher median number of baseline metastatic sites (3 vs 1, P < .001). IrAEs were similar between both groups (42% vs 38%), and no cardiac irAEs occurred in patients with pericardial effusions. PFS (median 5.6 vs 4.6 months, P = .3) and OS (median 10.2 vs 14.7 months, P = .50) were not statistically different between patients with pericardial effusions and the controls, respectively. In both multivariable and IPTW models, pericardial effusions were not associated with PFS or OS. Conclusions Among patients with NSCLC and pre-existing pericardial effusions, ICIs demonstrate meaningful clinical benefit similar to those without effusions, with no new cardiac or severe toxicities.

PURPOSE Systematic integration of tobacco cessation treatment within cancer centers is needed to improve smoking cessation outcomes among cancer patients and survivors. The current study characterizes baseline rates of tobacco use, use of cessation support, and changes in tobacco use over time among 756 participants diagnosed with cancer and enrolled in 9 ECOG-ACRIN Cancer Research Group trials. MATERIALS AND METHODS Participants completed surveys at trial enrollment and at 3- and 6-month follow-ups. Descriptive statistics were used to characterize patient characteristics and selected items from the Cancer Patient Tobacco Use Questionnaire (C-TUQ). Generalized estimating equations were used to examine the time point effect on tobacco product use. RESULTS At baseline, 11% of participants (n = 740) currently smoked cigarettes. Among participants with data available at all time points (n = 443), prevalence of current smoking was stable over time, with 7.2% of participants (n = 32) reporting current smoking at baseline, 7.0% (n = 31) at the 3-month follow-up assessment, and 6.8% (n = 30) at the 6-month follow-up assessment. Most participants (n = 77/104) who smoked cigarettes within the year prior to their cancer diagnosis continued smoking after their diagnosis, and during (n = 44/72) and following completion (n = 30/46) of their treatment. Sixty-two percent of participants (n = 81) who were currently smoking at baseline reported using smoking cessation medication and 32.1% reported use of nonpharmacologic smoking cessation support since their cancer diagnosis. In longitudinal analyses, the odds of using cigarettes since their cancer diagnosis, 3-month follow-up, and 6-month follow-up was higher than the odds of using cigarettes for the past 30 days at baseline (odds ratio [OR] = 1.97, OR = 1.62, and OR = 1.50, respectively; all p s < .01). CONCLUSION Smoking persists over time among patients with cancer enrolled in therapeutic cancer trials. Findings highlight the importance of increasing access to integrated and longitudinal smoking cessation support.

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of heterogenous hematologic malignancies characterized by the proliferation of blood cells and consist of myelofibrosis, polycythemia vera, and essential thrombocythemia. The NCCN Guidelines for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the aim of providing recommendations for the comprehensive care of adults with these diseases. The panel of experts convenes at least once a year to discuss requested changes to the Guidelines and to evaluate emerging data. These Guideline Insights focus on some of the recent updates for myelofibrosis.

The NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget’s disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Breast Cancer focuses on the recommendations for the management of recurrent or stage IV (M1) metastatic breast cancer. It summarizes the treatment strategies stratified by tumor biology, including hormone receptor status and HER2 expression, as well as clinical factors such as prior therapy and disease-free interval. Throughout all treatment lines, supportive care, quality of life preservation, toxicity minimization, and clinical trial participation are emphasized as integral components of patient care.

Glioblastoma (GBM) is a devastating cancer with a dismal prognosis. Current treatment includes temozolomide (TMZ), which is more effective in about 50% of GBMs that have O 6 - methylguanine DNA methyltransferase ( MGMT ) promoter methylation. MGMT is a DNA repair protein that reverses TMZ-induced DNA damage. EGFR is a prime oncogene in GBM. Here, we report that EGFR inhibition induced the down-regulation of MGMT in GBM cells, revealing a previously unidentified link between EGFR signaling and response to TMZ. EGFR inhibition led to activation of two transcription factors, activator protein-1 (AP-1), which repressed MGMT transcription, and nuclear factor κB (NF-κB), which up-regulated MGMT transcription. EGFR inhibition also induced AP-1–mediated transcription of miR-616. miR-616 inhibited both MGMT translation and NF-κB activation. Thus, the overall effect of EGFR inhibition was down-regulation of MGMT expression. In addition, we provided an explanation for the prior failure of clinical trials that used concomitant EGFR tyrosine kinase inhibitors (TKIs) and TMZ. TMZ up-regulated MGMT, and concomitant treatment with EGFR TKIs and TMZ failed to down-regulate MGMT. However, pretreatment with EGFR TKIs followed by TMZ efficiently down-regulated MGMT and enhanced TMZ sensitivity in experimental models. Posttreatment tumor tissues from two clinical trials were used to validate these findings. We demonstrated that EGFR inhibitors induced down-regulation of MGMT in posttreatment resected tumor tissues from patients with GBM and the failure of EGFR inhibition to down-regulate MGMT if TMZ was used concomitantly. These data support using EGFR TKIs before TMZ treatment as a therapeutic approach in MGMT unmethylated GBM.

Abstract Hemorrhagic shock is a common emergency that accounts for more than 10% of global mortality and up to 40% of trauma-related mortality. The Advanced Trauma Life Support (ATLS) guidelines outline resuscitation strategies in patients with massive hemorrhage based on clinical trial and observational data. Early intervention with fluids and/or blood products is recommended during resuscitation as key to maintaining vascular patency, stabilizing a patient’s blood pressure, maintaining tissue oxygenation, and limiting shock. From a transfusion perspective, there is wide heterogeneity in the quality of blood products due to donor and manufacturing variation. The optimal transfusion strategy for massive hemorrhage remains unclear. In silico models of resuscitation may offer a means to evaluate the effectiveness and safety of various resuscitation protocols. Here we describe a stochastic multicompartment model of fluid balance and resuscitation that includes (i) cardiovascular hemodynamics, (ii) body fluid compartments and capillary solute exchange, (iii) the ability to alter hemorrhage, resuscitation, and hemostasis parameters, and (iv) tissue oxygenation and capillary-alveolar gas exchange. Building upon deterministic frameworks, this stochastic model more faithfully reflects the clinical heterogeneity of bleeding patients at a level I trauma center. This allows for a proof of concept in silico trial comparing crystalloids, conventional component therapy (CCT), i.e. red cell, platelet and plasma components, to cold-stored low titer group O whole blood (LTOWB). In an in silico cohort of ATLS class III (>30% and ≤40% blood volume lost) hemorrhage, LTOWB resuscitation reduced the time spent in the critical hemostatic window (platelet count <50x109/L, INR≥2, hemoglobin (Hgb) <8 g/dL and fibrinogen <150 mg/dL) compared with CCT (90.59 vs. 147.62 minutes; p=0.04), with no difference in predicted event-free survival (t = 240 minutes; cardiac < 1.5, fluid overload > 10% or SBP > 150% of the starting SBP, or Hgb < 3.0 g/dL). In a separate cohort of ATLS class IV (>40% blood volume lost) hemorrhage, LTOWB yielded a higher predicted event-free survival (74%) versus the CCT arm (69%, p < 0.01). We demonstrate how this in silico platform can function as a digital twin for hemorrhagic trauma enabling precision transfusion strategies, and in parallel, an operational twin to support blood banks to forecast blood product demand and inform massive transfusion protocols and clinical trial design.

Abstract Problem Statement Communication failures in critical care contribute to preventable medical errors, impaired team performance, and unsafe care environments. Despite recognition of its importance, communication training for fellows remains inconsistent across hierarchical (ICU) and non-hierarchical (research/QI) environments. This variability limits fellows’ ability to adapt communication strategies, affecting clinical decision making and collaboration. Existing curricula often lack experiential rehearsal and cross-context transfer, leaving trainees underprepared to communicate across settings. Targeted Needs Assessment A pre-course focused assessment of critical care fellows at a single center revealed heterogeneity in formal communication training and confidence in applying communication strategies across team structures. Peer feedback identified gaps in negotiation, nonverbal cue recognition, and role clarity. Primary Goal Equip critical care fellows to communicate with intentional presence and professionalism across hierarchical and non-hierarchical clinical settings. Objectives Implement a one-day curriculum aligned with ACGME Critical Care Medicine milestones and CCF HRO (High Reliability Organization) principles. - Demonstrate effective active listening and closed-loop communication - Identify and respond to verbal and nonverbal cues - Exhibit leadership behaviors promoting psychological safety - Adapt communication strategies across team structures Educational Strategies and Curriculum Design Curriculum planning involved interdisciplinary meetings between critical care faculty, simulation education specialists, curriculum leads, and improvisation specialist. Design aligned with adult learning and simulation best practices. The curriculum integrated three educational approaches 1) Improvisational communication training emphasizing inclusive language and nonverbal cue awareness 2) Narrative reflection and professional identity formation 3) High fidelity simulation using communication-intensive ICU and non-ICU scenarios. Simulation scenarios included a) Dual patient respiratory failure and cardiac arrest requiring role assignment and closed-loop communication b) Plane crash survival lab requiring group consensus without assigned leadership Implementation and Learner Evaluation Eleven of twelve critical care medicine fellows participated. Pre and post-course surveys assessing communication confidence across settings were completed by all participants. Faculty observation rubrics assessed communication behaviors. Key Outcomes/Results (see graphs) Substantial increases in communication confidence were observed across hierarchical ICU and non-hierarchical environments. Fellows agreed that communication competency should be a required component of training. High impact elements included a) Improvisational communication techniques integrated with simulation b) Nonverbal communication awareness c) Adoption of inclusive language d) Psychological safety e) Improved professionalism and interdisciplinary communication consistency Conclusion and Next Steps This improvisation-enhanced simulation curriculum improved fellows’ confidence communicating across hierarchical and non-hierarchical settings. Next steps include incorporating cognitive load management training; the curriculum is adaptable to external audiences and supports organizational HRO principles. This abstract is funded by: N/A