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.

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 Background: Prostate cancer (CaP) is among the most common cancers in U.S. men, with Black men experiencing a 1.7-fold higher incidence and nearly twice the mortality rate compared with non-Hispanic White men. While early detection has improved survival, differences remain in recovery and quality of life (QoL). Sexual dysfunction after treatment affects identity, relationships, and well-being, yet stigma, cultural norms, and limited access to patient-centered care prevent open discussion. Few initiatives address the intersection of identity, stigma, and survivorship in this population. Community town halls provide a trusted, culturally responsive space for shared learning, peer connection, and open dialogue on survivorship and sexual health. Methods: Two community-engaged CaP town halls were convened by the Multidisciplinary Health Outcomes Research and Economics (MORE) Lab at the University of Oklahoma Health Campus (OUHC) to explore survivorship issues among Black CaP survivors. The first, held virtually in June 2024, included watch parties in Georgia and Texas. The second, in November 2024, was hybrid, hosted at OUHC and via Teams with a watch party at the Willa D. Johnson Recreation Center, a community center in Oklahoma City. Panelists included oncologists, psychologists, survivors, partners, and Community Advisory Board members. Both town halls featured survivor storytelling, provider Q&A, and interactive discussion. Post-event surveys captured demographics, satisfaction, and impact. Open-discussion transcripts were analyzed using Braun and Clarke’s reflexive thematic analysis, guided by a constructivist framework. Results: A total of 124 participants attended both town halls. Survey respondents (n=17; 13.7%) provided demographic and satisfaction data; remaining insights came from all participants who engaged in open dialogue. Respondents ranged in age from 19-76 years (mean=48.7 ± 21.8). Of the 17 respondents, 93% rated the events as very good or excellent; 23.5% were CaP survivors, all identifying as Black. Five themes emerged: (1) Masculinity, stigma, and silence limit help-seeking; (2) Sexual dysfunction and identity loss cause major emotional burdens; (3) Navigation challenges highlight systemic barriers; (4) Spousal and psychological support aid coping; and (5) Survivorship empowerment. Participants valued hearing “real stories from real men,” validating their experiences. Conclusions: Community town halls are a feasible and culturally relevant strategy to engage Black CaP survivors in survivorship and sexual health discussions. By centering lived experiences and facilitating two-way communication between survivors, clinicians, and researchers, these events build trust and reduce stigma. Future work will assess changes in knowledge, engagement, and confidence in care navigation and explore scaling this community-academic model to improve survivorship QoL. Citation Format: Parisa Ghasemi, Gaurav Kumar, Ernest T. Kaninjing, Adanma Ayanambakkam, Yaw A. Nyame, Amy Siston, Jordan M. Neil, Adam C. Alexander, Andrew G. McIntosh, Yan Zhao, Zsolt Nagykaldi, Kathleen A. Dwyer, Mary Ellen Young, Sabrina Dickey, Daniel Morton, Opeyemi Bolajoko, Darla E. Kendzor, Motolani E. Ogunsanya. Survivorship and sexual health: What we learned from Black men in community town halls [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 2483.

Abstract Introduction: The intricate cellular structure is a constantly evolving environment where cells interact, communicate, and adapt to their surroundings. The fate, role, and actions of each cell are shaped by its specific location within the tissue. Therefore, studying the spatial proteome is crucial for gaining a deeper understanding of physiological or pathological processes. With significant advancements in microscopy and mass spectrometry, it has become feasible to explore the cellular proteome at low or even single cell numbers. However, spatial proteomics is an evolving field with scope for newer sample preparation and data analysis techniques. Our objective was to develop a sample preparation workflow for analyzing proteome from limited cells extracted from formalin fixed paraffin embedded (FFPE) tissue using laser capture microdissection (LCM). Methods: One hundred cells from the FFPE normal colon tissue were extracted by LCM and collected into an AFA-compatible 96-well plate. Decrosslinking was performed at 900C for 50 minutes followed by lysis in a buffer composed of 100 mM triethylammonium bicarbonate and 0.1% n-dodecyl-β-D-maltoside using adaptive focused acoustic (AFA) energetics in scanning mode for 5 minutes. After lysis, the proteins were digested using Trypsin/Lys-C mix using AFA energetics for 1 hour. The resulting peptides were acidified with trifluoroacetic acid and analyzed on a timsTOF Ultra 2 mass spectrometer coupled to a nanoElute 2 liquid chromatography system using a 15 cm (75 μm) IonOpticks column, in DDA-PASEF mode for a total run time of 34 minutes. The data were searched against the UniProt Human Reviewed protein database using MSFragger. Results: We utilized AFA energetics to extract and digest proteins from a limited number of cells isolated from FFPE tissue using LCM. This experiment was conducted with technical replicates to ensure accuracy and reliability. A total of 3,723 proteins were identified across the three replicates, with replicate 1 identifying 3,895 proteins, replicate 2 identifying 3,754 proteins, and replicate 3 identifying 3,519 proteins. In total, we identified 21,005 peptides, with replicate 1 identifying 22,896 peptides, replicate 2 identifying 22,377 peptides, and replicate 3 identifying 17,741 peptides from 100 colon cells. Notably, we observed a 70% overlap in the proteins identified across the three replicates, which highlights the reproducibility of the approach. Conclusion: The entire sample preparation process, after cell collection, was completed within a concise four-hour timeframe, demonstrating the efficiency of this methodology for analyzing protein profiles from small cell populations. Further, this approach is highly adaptable to automation and high-throughput applications. Its adaptability and scalability make it a promising strategy for spatial proteomics applications. Citation Format: Dong-Gi Mun, Kiran Mangalaparthi, Daigo Gunji, Amy J. French, Raghavendra Pasupuleti, Cristine Charlesworth, Sameer Vasantgadkar, DEB BHATTACHARYYA, Akhilesh Pandey. An AFA assisted workflow for mass-spectrometry based proteomics of FFPE samples [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 7657.

Abstract Background: Hypogammaglobulinemia at the time of CLL diagnosis predicts shorter time to first therapy (TTFT). However, the depth of immunoparesis and its impact on TTFT in newly diagnosed MBL/CLL remains unexplored. Methods: We identified previously untreated MBL/CLL patients from Mayo Clinic CLL Database (2000-2024) who had serum immunoglobulin (Ig; IgG, IgM and IgA) and monoclonal protein assessed within 1 year of diagnosis. Immunoparesis was evaluated: a) qualitatively by classifying patients into preserved, partial and full Ig suppression, based on the number of suppressed Igs; and b) quantitatively by calculating the average relative difference (ARD), defined as the mean percentage below normal for all Igs. For both methods, only uninvolved Igs were considered for those with monoclonal protein. TTFT was estimated by Kaplan-Meier with competing risk of death. Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI). Results: Among 1420 patients, median age at diagnosis was 65 (range 28-96); 954 (67%) were male; 493 (44.8%) had unmutated IGHV, and 86 (6.8%) had TP53 disruption. The median [range, mg/dL] serum IgG, IgA, and IgM were 889 [111-5290], 132 [1-4880], and 49 [4-9480]. Low IgG was present in 472 (33.2%), low IgA in 223 (16.4%), and low IgM in 530 (37.3%) patients. An M-spike was detected in 122 (8.6%) patients; distribution was: IgG (73), IgM (30), IgA (6), or multiple (13). By qualitative assessment, preserved Ig were seen in 664 (46.8%), partial Ig suppression in 604 (42.5%), and full suppression in 152 (10.7%) patients. By quantitative assessment, median ARD was 0.6 (-0.8 to 11.3); 280 (19.7%) patients had negative ARD, and 1140 (80.3%) had positive ARD. In those with negative ARD, 128 (9%) had partial Ig suppression and 152 (10.7%) had full Ig suppression; in those with positive ARD, 664 (46.8%) had preserved Ig and 476 (33.5%) had partial Ig suppression. Median follow-up was 14.7 years; 510 patients progressed requiring therapy. Median TTFT was 9.6 years. Median TTFT for patients with preserved Ig was 12.6 years, 8.0 years for partial Ig suppression (HR 1.4, 95%CI 1.1-1.7), and 1.8 years for full Ig suppression (HR 3.1, 95%CI 2.4-4.0). The median TTFT was 2.3 and 12.1 years for patients with negative vs positive ARD; negative ARD was associated with shorter TTFT (HR 2.4, 95%CI 2.0-2.9). After adjusting for sex and CLL-International Prognostic Index (CLL-IPI) score, full Ig suppression (HR 2.9, 95%CI 2.2-3.9) and partial Ig suppression (HR 1.6, 95% CI 1.3-2.0) were associated with shorter TTFT (model 1, c-stat 0.77); and negative ARD (HR 2.4, 95%CI 2.0-2.9) was associated with shorter TTFT (model 2, c-stat 0.76). Negative ARD identified an additional 9% of patients at higher risk for shorter TTFT beyond full Ig suppression. Conclusions: The depth of immunoparesis at diagnosis predicts TTFT and enhances risk stratification in newly diagnosed MBL/CLL. Citation Format: Yuan Yao, Kari G. Rabe, Eli Muchtar, Paul Hampel, Yucai Wang, Lindsey Roeker, Saad Kenderian, Amber Koehler, Catherine Wagner, Amy Behnken, Jose F. Leis, Mazie Tsang, Talal Hilal, Ricardo Daniel Parrondo, Susan M. Schwager, Min Shi, Curtis A. Hanson, Celine M. Vachon, Shaji Kunnathu Kumar, Esteban Braggio, Neil E. Kay, Susan Slager, Sameer A. Parikh. Depth of immunoparesis predicts time to first therapy in newly diagnosed monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia [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 1191.

Importance The management of infectious and inflammatory lesions of the breast remains controversial. The expert panel focused on management recommendations for 3 of the most common infectious breast conditions, as very few evidence-based guidelines for the management of these conditions exist. Observations Clinicians should distinguish between infectious and noninfectious lactational mastitis (LM) because the former often requires interventions whereas the latter requires supportive care only. Patients with infectious LM often have thick fluid collections that are not amenable to aspiration and usually require a stab incision with drain placement (but no packing) to resolve the infection. Operative drainage is only required if the patient cannot tolerate an office procedure. If a phlegmon is present, antibiotics should be prescribed for at least 10 days. The diagnosis of granulomatous mastitis (GM) requires pathology confirmation with characteristic findings on core biopsy. Cystic neutrophilic granulomatous mastitis (CNGM) is a specific form of GM associated with a granulomatous reaction to Corynebacterium infection and should be empirically treated with doxycycline. For patients without findings characteristic of CNGM and no other associated bacterium identified, there is no role for empiric antibiotic use. Granulomatous mastitis cases often recur and can take up to 18 months to resolve. Patients who have GM cases with worsening symptoms should be treated with repeated intralesional steroid injections; surgical excision or repeated aspirations should be avoided. Cases refractory to intralesional steroid injection may require oral steroids or even advanced biologic agents such as methotrexate or azathioprine. Periductal mastitis with squamous metaplasia of lactiferous ducts (PDM-SMOLD) is a distinct entity from other periductal mastitis cases that can present with recurrent abscesses and should be treated with antibiotics and aspiration for fluid collections. Operative excision for PDM-SMOLD is required for those patients who present with a fistula or recurrent episodes typically using a radial incision to remove the diseased ducts within and below the nipple. Conclusions and Relevance Evidence-informed, consensus-, and expert opinion–based guidelines for the management of infectious and inflammatory conditions of the breast were developed. Clinicians can use these guidelines to appropriately manage these conditions for which clinical care often varied in the past.

Background: Statins have been associated with a reduced risk of primary liver cancer (PLC), primarily hepatocellular carcinoma (HCC). However, the optimal use for effective protection and whether benefits vary by patient characteristics remain unclear. We evaluated the association between statin use and PLC risk in metabolic-dysfunction-associated steatotic liver disease (MASLD), considering cumulative exposure and potential effect modifiers. Methods: We conducted a retrospective cohort study using the Veteran Affairs electronic health records. Patients with chronically elevated liver enzymes and metabolic dysfunction, without other chronic liver diseases, were identified between 2007 and 2009 and followed through 2019 for incident PLC. Statin exposure was assessed at baseline and during the follow-up, with dose standardization by LDL-lowering potency (simvastatin-equivalent units). Time to PLC was analyzed using Cox models adjusted for covariates, considering potential interactions. Results: Among 329,577 patients (92% male; median age 62 years), 0.82% developed PLC (median follow-up of 9.7 years). Baseline statin use showed a significantly lower PLC risk (adjusted hazard ratio 0.64; 95% CI, 0.57–0.71; p < 0.0001). No significant interaction was observed with age, sex, metabolic syndrome, or cirrhosis. Higher cumulative statin exposure demonstrated a dose-dependent risk reduction, remaining significant at simvastatin-equivalent doses > 15,561 mg annually after accounting for incident cirrhosis. Atorvastatin/rosuvastatin use provided comparable protection, despite different lipophilicity, and demonstrated stronger effects than others. Conclusions: In MASLD, statin therapy was associated with a dose-dependent PLC risk reduction. High-intensity therapy (simvastatin-equivalent > 40 mg daily) conferred substantial protection regardless of age, sex, insulin resistance, or cirrhosis, supporting a potential statin-based PLC chemoprevention in MASLD.

ABSTRACT The normal adult male breast has not been characterized at single-cell resolution, leaving the cellular basis of male breast cancer (MBC) biology undefined. Here we present an integrated single-cell RNA sequencing atlas of the adult human breast comprising 174,471 cells from 17 donors (3 male, 14 female), including 18,117 male-derived cells. This revealed that the male breast retains all three epithelial populations, basal (BC), luminal progenitor (LP), and luminal committed cells (LC), but with an increase in LC at the expense of BC and LP across all three male donors. Male LC were distinguished from female by elevated ESR1 and PGR mRNA, enrichment of RNA processing and ribosome biogenesis programs, reduced inflammatory cytokine and growth factor signaling, elevated estradiol gene set enrichment scores, and higher inferred activity of developmental patterning transcription factors. This pattern was observed across differential expression, gene ontology, ligand profiling, and regulon-based analyses, and was not restricted to sex chromosome-linked gene expression. This is consistent with the near-universal estrogen receptor (ER) positivity that characterizes MBC clinically. This atlas provides the first cellular and transcriptional reference for the normal male breast and a resource for investigating sex differences in mammary biology, germline susceptibility variant interpretation, and modeling breast malignancies.