Citations

These NCCN Guidelines for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. They are intended to assist oncology teams to identify patients who require referral to psychosocial resources and to give oncology teams guidance on interventions for patients with significant distress. These guidelines also provide guidance for social workers, certified chaplains, and mental health professionals by describing treatments and interventions for various psychosocial problems as they relate to patients with cancer. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding standards of care for distress management in patients with cancer and implementation of these standards, including application of evidence-based care delivery models, such as the collaborative care model.

Background: Chronic hip abductor insufficiency remains a challenging problem to treat and can result in significant disability in some patients. Tendon transfers involving the gluteus maximus (GM) or combined GM with tensor fascia latae (GM+TFL) are common options for surgical reconstruction. The purpose of this systematic review was to compare clinical outcomes, complications, and revisions rates of patients who underwent GM transfer or GM+TFL transfer for irreparable hip abductor tears. Methods: PubMed (MEDLINE), Scopus (EMBASE, MEDLINE, COMPENDEX), and Cochrane databases were used to conduct a systematic review of articles from inception to February 2025. A total of 18 studies were included (11 GM transfer, 7 GM+TFL transfer). Demographics, hip setting (native hip, primary total hip arthroplasty [THA], revision THA), patient-reported outcome measures, presence of Trendelenburg gait, abduction strength, complication rates, and revision rates were analysed. Results: A total of 207 patients (208 hips) underwent GM transfer, while 55 patients (55 hips) underwent GM+TFL transfer. Meta-analyses demonstrated that both techniques yielded significant preoperative to postoperative improvements in modified Harris Hip Scores/Harris Hip Scores and Visual Analogue Scale pain scores ( p < 0.001). In total, 33.9% of patients who underwent GM transfer had a persistent Trendelenburg gait postoperatively, compared to 48.1% of those who underwent GM+TFL transfer. The complication rate was 16.8% (23/137) for patients who underwent GM transfer and 2.7% (1/37) for those who underwent GM+TFL transfer; while revision rates were 5.9% (9/152) and 3.6% (2/55), respectively. Conclusions: Both GM and GM+TFL transfers yielded comparable outcomes in patients with chronic hip abductor insufficiency not amendable to primary repair. The complication rate was substantially higher in patients who underwent GM transfer, whereas revision rates were comparably low for both techniques. In particular, a sizeable proportion of patients continued to exhibit a persistent Trendelenburg gait postoperatively following both surgical techniques, highlighting the complexity of this pathology. PROSPERO registration number: CRD420251002466

Abstract Background: Hepatocellular carcinoma (HCC) is largely refractory to immune checkpoint blockade due to immune exclusion, stromal barriers, and aberrant vasculature. We evaluated whether multimodal therapy - external beam radiotherapy (EBRT) for antigen release, intratumoral dendritic cell (DC) vaccination for antigen presentation, PD-L1 blockade for immune activation, and VEGF inhibition for vascular normalization - could convert “cold” HCC tumors into sustained immune-inflamed states. Methods: Serial biopsies (baseline, post-EBRT, end-of-treatment [EOT], and progression [PD] when available) from three patients enrolled in an ongoing phase II trial (NCT03942328) underwent multiplex immunofluorescence, spatial neighborhood analysis, and transcriptomic profiling. Longitudinal changes in cellular composition, immune-stromal architecture, spatial contact networks, and pathway activity were compared. Results: Baseline tumor microenvironments (TMEs) were strongly immune-excluded, dominated by tumor (PanCK+60-70%) and stroma (SMA+/Vimentin+25-30%) with sparse immune infiltration (&lt;10-15%). Post-therapy, immune complexity and spatial connectivity increased 2-3-fold in all patients. Patient 1 showed robust cold-to-hot conversion with CD8+(3x), CD4+(2.2x), and DC (2.3x) expansion, increased CD8-DC interactions (2.5x), and reduced tumor fraction (-40%). Transcriptomics showed marked upregulation of IFN-γ (↑3.4x), HLA-DRA (↑2.7x), and reductions in VEGFR2 (↓50%) and HIF1A (↓40%), consistent with vascular normalization. Patient 2 exhibited stromal/vascular remodeling and improved T-cell infiltration but restricted immune diversity, with CD4+/CD8+ dyads (↑2.2x) and B/NK cells(↓ 60%). Neighborhood diversity rose (3→7 communities) and immune-tumor proximity improved (distance ↓ 35%). Patient 3 showed transient inflaming with CD8+(↑3x), DC(↑2x), and new CD4-CD20/CD4-CD56 interactions, followed by relapse marked by stromal/myeloid re-expansion (SMA+↑1.8x, CD14+↑2.5x), angiogenic resurgence (VEGFR2/CD34+↑2.2x), contraction of immune networks, and genomic shift from activating CTNNB1 mutation loss to ATM gain. DCs accumulated but localized mainly to DC-DC or DC-myeloid niches, indicating non-productive antigen presentation. Conclusions: Multimodal EBRT+DC+PD-L1/VEGF blockade induces four-sided synergistic TME reprogramming - antigen release, immune priming, checkpoint release, and vascular normalization - promoting cold-to-hot conversion in HCC. Durable inflaming correlates with sustained T-cell/DC expansion and vascular remodeling, whereas relapse reflects stromal/myeloid reinforcement and genomic adaptation. These findings define mechanistic trajectories of TME remodeling and highlight actionable barriers to sustained immunotherapy response in HCC. Citation Format: Lionel Aurelien Kankeu Fonkoua, Christopher L. Hallemeier, Basim Salem, Arina Tkachuk, Kaitlynn McCay, Panwen Wang, Ying Li, Thomas D. Atwell, Krishan R. Jethwa, Caitlin Conboy, Nguyen H. Tran, Leslie A. Washburn, Melody Wu, Chen Wu, Andre De Menezes Silva Corraes, Rondell P. Graham, Jose Caetano Villasboas, Kevin Regan, Zuoyi Shao, Rayaan Kamal, Nathan R. Foster, Haidong Dong, Sean Park, Yi Lin, Lewis R. Roberts. Multimodal immunotherapy remodels the tumor microenvironment in hepatocellular carcinoma: Integrative spatial and transcriptomic profiling from a Phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7935.

Abstract Background: Glioblastoma recurrence is inevitable despite aggressive surgical resection of contrast enhancing (CE) tumor. Unlike the deep molecular characterization of CE glioblastoma, unresected infiltrating tumor, representing minimal residual disease (MRD) has not been well profiled. Increasingly, clinical trials are being conducted in the MRD setting for glioblastoma patients, necessitating understanding of unresected infiltrating tumor for targeted therapeutic development. Methods: Visium HD spatial transcriptomics was used to profile a cohort of newly diagnosed, treatment-naïve glioblastoma patients that underwent supramaximal resection, with both core and infiltrating in situ components. Spatial profiles generated expression signatures of infiltrative and CE tumor. For in silico prediction of therapeutics targeting the MRD, expression signatures of infiltrative and CE tumor were compared with drug perturbation signatures from the NIH L1000 database using the sRGES method to predict reversal of disease expression patterns. IC50 data from human cell lines were aggregated from the Genomics of Drug Sensitivity in Cancer or individual study data while blood-brain barrier (BBB) penetrance was predicted using the CNS-MPO approach. Findings: Infiltrative tumor expression profiles were enriched for genes corresponding to neural and oligodendrocyte progenitor like cells. In contrast CE glioblastoma displayed mesenchymal and astrocytic programs, suggesting spatial concentration of glioblastoma states within MRD and CE tumor. For CE glioblastoma, proteasome inhibitors and glucocorticoid receptor agonists were predicted to have the highest antitumor activity. In contrast, histone deacetylase inhibitors (HDACi) were highly ranked for MRD while exhibiting low predicted efficacy in CE tumor. Synergy analysis of drug candidates provided multiple dual treatment options for both the CE and MRD contexts. Conclusions: Cumulatively, these data indicate that the resected tumor does not reflect the MRD state, providing clarity on why targeted therapeutics for glioblastoma have not been particularly successful. Spatial profiling of the MRD demonstrates vulnerability to unique drug targets, which if utilized in the correct setting could confer greater survival benefit. Citation Format: Harrshavasan Congivaram, Shashwat Tripathi, Mateo Gomez, Katy McCortney, Ching Man Wai, Ruochen Du, Thomas K. Sears, Jianzhong Zhang, Daniel J. Brat, Craig M. Horbinski, Mark W. Youngblood, Jared T. Ahrendsen, Adam M. Sonabend, Stephen T. Magill, Matthew C. Tate, Maciej S. Lesniak, Sean Sachdev, Timothy Sita, Priya Kumthekar, Karan Dixit, Robin Buerki, Ditte Primdahl, Mustafa Khasraw, John de Groot, David A. Reardon, Rimas V. Lukas, Roger Stupp, Amy B. Heimberger. In silico screening of therapeutics candidates targeting minimal residual disease in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2496.

Abstract Introduction: Liver cancer remains a leading cause of cancer mortality globally with limited treatment options for patients (pts) with unresectable hepatocellular carcinoma [HCC] and intrahepatic cholangiocarcinoma [iCCA][1,2,3,4]. We hypothesize that combining the intratumoral dendritic cell (DC) vaccination after external beam radiotherapy (EBRT) without (phase I) and with (phase II) systemic atezolizumab and bevacizumab (atezo/bev for HCC) would enhance tumor-specific immunity and improve clinical outcomes, and present preliminary results from our phase I/II trial (NCT03942328). Methods: Peripheral blood mononuclear cells (PBMCs) were collected at baseline (PRE), after radiation (EBRT), and after completion of DC without or with atezo/bev (POST). Single-cell RNA sequencing with TCR sequencing were analyzed using CellRanger v7.0.1, Immunopipe, Seurat v5.3.0, & Gene-set enrichment analysis (GSEA). Long EFS (EFS-L) is defined as &gt;=12 months (mo) for phase I and &gt;=18mo for phase II, and short EFS (EFS-S) below that. Results: Seventeen patients have been analyzed to date (Phase I: n=8 [4 HCC, 4 iCCA]; Phase II: n=9 HCC). 674,106 cells were sequenced (146,843 PRE; 168,838 EBRT; 114,437 POST). GSEA for EFS-L vs EFS-S were comparable at PRE, EBRT and POST between phase I and phase II. EFS-S was associated with enrichment of interferon alpha (IFNα; B naïve, monocytes, pDC, cDC2, NK, Treg, CD8 Tcm and Tem at PRE and POST; B intermediate, CD4 Tem and NK at EBRT) and reactive oxygen species (ROS; PRE: pDC, CD8 Tcm, Tem. EBRT: CD4 Tem. POST: CD8 T naïve Tem, CD4 Tcm & Tem, cDC2) pathways. In contrast, EFS-L was associated with enrichment of WNT-β-catenin (WNT; CD14 mono at EBRT & POST, B intermediate at EBRT), TGFb (PRE: NK; EBRT: B intermed, CD4 Tem; POST: monocytes, CD4 naïve & Tem, pDC, cDC2), and angiogenesis (EBRT: NK; POST: monocytes, cDC2) pathways. Interestingly, enrichment of protein secretion pathway in NK cells was associated with EFS-L, but among other cells were associated with EFS-S (PRE: CD16 mono, Treg; POST: CD16 mono, CD4 & D8 Tem). Compared to phase I, addition of atezo/bev in phase II pts was associated with a significant increase in Gini coefficient (p&lt;0.0001), suggesting expansion of certain TCR clones, along with a trend for increased Gini coefficient from Pre to Post in both phase I and II. Conclusions: Preliminary analysis of this study combining EBRT with intratumoral DC vaccination +/- PD-L1/VEGF blockade identified distinct treatment-related changes in systemic cellular immune profiles. Enhanced TCR clonal diversity in phase II suggests added immunologic benefit from PD-L1/VEGF blockade. As accrual continues, integrated analyses will identify systemic immune correlates of clinical benefit and resistance to this multimodal immunotherapy approach. Citation Format: Melody Wu, Panwen Wang, Chen Wu, Ying Li, Christopher L. Hallemeier, Thomas D. Atwell, Nguyen H. Tran, Andre de Menezes Silva Corraes, Kevin Regan, Zuoyi Shao, Rayaan Kamal, Haidong Dong, Lewis R. Roberts, Sean Park, Yi Lin, Lionel Aurelien Kankeu Fonkoua. Radiation-dendritic cell combination therapy drives systemic cellular immune shifts in liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3741.

Abstract Background: Personalizing chemoradiotherapy (chemoRT) for locally advanced non-small cell lung cancer (LA-NSCLC) is limited by the lack of early biomarkers that inform response during treatment. Current circulating tumor DNA (ctDNA) molecular residual disease assays predict post-treatment outcomes but lack mid-treatment utility. ctDNA burden estimation has traditionally relied on variant-centric metrics such as maximum variant allele fraction (Max VAF), which rely on mutation-specific signals and may be confounded by histology-dependent shedding variability, allelic imbalance, and clonal hematopoiesis. Here we present circulating tumor fraction estimate (ctFE), a machine-learning composite score that integrates VAF distributions, copy-number alterations, and germline B-allele frequency deviations to approximate global tumor burden using a widely available, tumor-naïve clinical platform. Methods: A burden-based ctFE threshold was derived using pre-treatment plasma from a prospective phase II clinical trial of MR-guided hypofractionated chemoRT (LA-WU, n=26), locked, and applied unchanged to early mid-treatment samples (day 10-14). To test scalability and generalizability, its prognostic performance was validated in two real-world cohorts: 94 LA-NSCLC patients receiving definitive chemoRT (LA-RW) and 309 oligometastatic NSCLC patients receiving consolidative RT (OM-RW). ctFE and Max VAF were compared as continuous predictors across cohorts. Results: ctFE consistently outperformed Max VAF. In LA-WU, pre-treatment ctFE was associated with overall survival (OS HR=1.15, p=0.04) and progression-free survival (PFS HR=1.84, p=0.009), whereas Max VAF was not. Mid-treatment ctFE remained prognostic for PFS (HR=1.14, p=0.026). Early ctFE dynamics defined three molecular response groups with marked OS separation: consistently low, responder, and nonresponder groups (median OS 60.8 vs 13.0 vs 2.9 months, respectively; p&lt;0.001). In multivariable models including both biomarkers, higher ctFE remained independently associated with worse survival in LA-RW (OS HR=1.88, p=0.010) and OM-RW (OS HR=1.37, p=0.040; PFS HR=1.45, p=0.008), whereas Max VAF did not. The locked ctFE threshold stratified OS across all cohorts (LA-WU HR=5.93; LA-RW HR=9.08; OM-RW HR=2.26; all p&lt;0.001). Conclusion: ctFE provides clinically meaningful pre- and mid-treatment risk stratification and consistently outperforms Max VAF across locally advanced and oligometastatic NSCLC cohorts. We show that ctFE is a biologically informative, clinically generalizable and scalable ctDNA burden metric measurable using a tumor-naïve, off-the-shelf assay, supporting its practical utility in biomarker-adapted radiotherapy strategies. Citation Format: Ayesha Hashmi, Jessica Linford, Pradeep S. Chauhan, Kaushal Parikh, Rotem Ben-Shachar, John Guittar, Malvika Pillai, Jyoti Patel, Matteo Bergsagel, Nicholas P. Semenkovich, Kenneth R. Olivier, Sean S. Park, Dawn Owen, David M. Routman, Katie N. Lee, Alex D. Sherry, Aaron S. Mansfield, Daniel Morgensztern, Ramaswamy Govindan, Clifford G. Robinson, Carmen Bergom, Saiama N. Waqar, Bruna Pellini Ferreira, Gregory R. Vlacich, Aadel A. Chaudhuri. Early ctDNA quantification by ctFE outperforms Max VAF for survival stratification across locally advanced and oligometastatic NSCLC treated with radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1183.

Abstract Introduction: Ewing sarcoma (EwS) is a FET::ETS family member-driven primary bone cancer demonstrating vast heterogeneity. Between a patient’s primary diagnosis and disease progression, tumor cell state adaptation, microenvironment changes, and the landscape of evolving therapeutic vulnerabilities remain poorly understood. To address these gaps, the Sean Karl Cohort was established in 2025 to conduct the largest single-cell transcriptomic analysis of retrospective paired tumor samples from patients with EwS. Here, we present data from the five analytic teams, and through shared SOPs now expand this cohort to Europe. Methods: Common sample processing SOPs were established to isolate cells from FFPE material from paired patient EwS samples. Single-cell (sc) RNAseq was generated using the GEM-X Flex Gene Expression protocol (10x Genomics). Alex’s Lemonade Stand Foundation (ALSF) Data Lab established a common data processing and integration pipeline with an EwS-specific cell annotation workflow to create a harmonized dataset for downstream analyses. Analytic teams were created to define tumor cell subpopulations and their therapeutic vulnerabilities and to characterize the tumor microenvironment. Data: We demonstrate the feasibility of generating high-quality scRNAseq profiles from retrospective FFPE-preserved EwS tumors. To date, 116 samples have yielded ∼800,000 cells. Integrated analysis reveals reproducible EwS tumor cell states shared across patients with regulatory network analyses nominating candidate therapeutic vulnerabilities. The scale of this international cohort enables saturation analysis for rare cell populations. Paired and longitudinal samples further allow correlation of emergent cell states with therapy resistance and metastatic progression. For example, immune-focused analyses show increases in T cell and macrophage populations in post-therapy samples. A novel, standardized EwS-specific cell annotation workflow has been developed to harmonize analyses and findings. These data will be openly shared with the community through the ALSF Single-cell Pediatric Cancer Atlas Portal. Conclusion: Large-scale international collaborative sample sharing, standardized processing pipelines, and harmonized EwS-specific annotations now enable deep single-cell analyses to characterize tumor heterogeneity in this rare pediatric and adolescent cancer. An in vivo expansion of the Sean Karl Cohort is underway to assess conservation of EwS tumor cell states and regulatory vulnerabilities identified in human tumors pre- and post-therapy in preclinical models, further supporting translation of these findings toward therapeutic strategies. Citation Format: Abbe Pannucci, Elina Mukherjee, Jessica D. Daley, Shireen Sita Ganapathi, Elissa Boguslawski, Lea Surrey, Lauren Gutstein, Patrick Azar, Emily Stockfisch, Azfar Neyaz, Ivy John, Jennifer Picarsic, Yutaro Tanaka, Byron Butaney, Riaz Gillani, Brian D. Crompton, Katherine A. Janeway, Jaclyln Taroni, Jessica Davis, Damon Reed, Adam Shlien, Theodore W. Laetsch, Rajen Mody, Clémence Henon, Thomas G. Grünewald, Elizabeth R. Lawlor, Filemon Dela Cruz, Patrick J. Grohar, Jovana Pavisic, Ally Hawkins, Anthony R. Cillo, Kelly M. Bailey. The Sean Karl Cohort: An international single-cell RNAseq study of paired patient Ewing sarcoma specimens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 643.

ABSTRACT Objective To (1) validate GAD65‐ELISA detection and quantification for type 1 diabetes mellitus and autoimmune neurological diagnoses, (2) correlate ELISA results (reference range < 5 IU/mL) with established radioimmunoprecipitation assay (RIA; ≤ 0.02 nmol/L), and (3) define ELISA clinical utility and pitfalls. Methods Serum performance for diabetes (FDA‐cleared, undiluted) was verified, and neurological laboratory‐developed serum and CSF dilution protocols were validated to extend the reportable range beyond > 250 IU/mL. ELISA and RIA values were correlated, including established neurological RIA cut‐offs (serum ≥ 20 nmol/L; CSF any positive). Results ELISA met analytical criteria (precision, accuracy, sensitivity, specificity, reference range) in serum and CSF and was clinically equivalent to RIA for autoimmune diabetes. Neurological ELISA cut‐offs were established at 10,000 IU/mL (serum) and 100 IU/mL (CSF). Precision was better below 10,000 IU/mL (CVs < 20%) than above (CVs 30.8% serum; 26.5% CSF). ELISA–RIA correlation and agreement was stronger below the neurological cut‐off (R 2 = 0.89) than above (R 2 = 0.36). Positive agreement for RIA‐defined neurological disease was 100% in serum and CSF; all serums were > 10,000 IU/mL. Clinical specificity was 97.5% in serum and 100% in CSF, exceeding reported RIA specificity. Screen results > 250 IU/mL spanned a wide range of dilution values; many were below the neurological cut‐off. Most patients with paired serum/CSF positivity showed elevated GAD65 IgG indices. Interpretation GAD65 ELISA and RIA have equivalent sensitivity for autoimmune diabetes and neurological testing, with higher specificity for ELISA. A serum cut‐off of 10,000 IU/mL is informative but requires clinical context, and dilution of screen > 250 IU/mL samples is essential for neurological interpretation.