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ADAPT-M: A tool to predict individualized benefit from adjuvant anti–PD-1 (PD-1) in resected high-risk melanoma.
Silva, Ines Esteves Domingues Pires da, Puig, S, Malvehy, Josep, Lebbe, Celeste, Meda, Laetitia Da , Leiter, Ulrike M., Vincent, T., Kaehler, Katharina C., Nalabothu, Rishitha, Khaddour, Karam , Huerta, Luis Paul Del Carpio, Grynberg, Shirly , Carlino, M S, Adegoke, Nurudeen A., Menzies, A, Long, Georgina V., Long, Georgina V. , Long, Georgina V , Grynberg, Shirly , Puig, Susana , Malvehy, Josep , Podlipnik, Sebastián , Stoff, Ronen , Hieken, Tina J. , Lebbé, Célèste , Leiter, Ulrike , Ma, Vincent The-Luc , Boutros, Andrea , Carpio, L.P. del , Carlino, Matteo S. , Menzies, Alexander M

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 9567-9567

10.1200/jco.2026.44.16_suppl.9567 Get It

9567 Background: Resected stage IIB/C and microscopic stage IIIA/B/C/D melanoma presents a significant risk of recurrence risk of 37 to 62% at 5 years (yrs). While 1 year of adjuvant PD1 therapy reduces this risk by approximately half, the individual patient’s baseline risk without treatment and their specific benefit from adjuvant PD1 remain unknown. We aimed to generate two separate predictive models for recurrence – one for untreated and one for treated pts - to calculate the individualised benefit of adjuvant PD1. Methods: Pts with resected stage IIB/C or microscopic stage IIIA/B/C/D melanoma, either treated with adjuvant PD1 or untreated at 13 major melanoma centres, and with at least 2 years of follow-up from surgery were included. We analysed pts demographics, disease characteristics, blood parameters, pathological and imaging data at baseline, and clinical outcomes. Propensity scores were estimated using logistic regression with covariates associated with treatment in univariate screening (p<0.05). Separate penalised multivariable logistic regression models were built to predict recurrence for treated and untreated pts. A tool based on these models was created to calculate the individual patient benefit from adjuvant PD1. Results: A total of 3560 pts was included, divided into untreated (discovery n=2384 and validation n=597) and treated (discovery n=404 and validation n=175) cohorts. The model for untreated pts included age, gender, primary site, histological subtype, Breslow thickness, ulceration, mitosis, number and site of regional lymph nodes (LN), mutation status and LDH (AUC 0.70 in discovery, 0.69 in validation). The model for treated pts included age, gender, Breslow thickness, site of regional LN, and mutation status (AUC 0.69 in discovery, 0.61 in validation). ADAPT-M (ADjuvant Anti-PD-1 Tool for Melanoma) calculates the individualized benefit of adjuvant PD1. For example, patient A, a woman ≤45 years old with a primary head & neck melanoma (superficial spreading, thickness >1-2 mm, no ulceration, 1 mitosis/mm 2 ), 2 clinically occult LN metastases in the neck, NRAS mutant, and normal LDH, has a 12-month recurrence risk of 21.9% untreated vs 2.3% treated (benefit 19.6%), and a 24-month risk of 41.1% untreated vs 6.4% treated (benefit 34.7%). While, patient B, a man ≤45 years old with a primary melanoma in the lower limb (nodular, thickness >1-2 mm, no ulceration, 1 mitosis/mm 2 ), 2 clinically occult LN metastases in the groin, BRAF V600 mutant, and normal LDH, has a 12-month recurrence risk of 14.2% untreated vs 11.8% treated (benefit 2.5%), and a 24-month risk of 28.0% untreated vs 30.1% treated (no benefit). Conclusions: ADAPT-M, a clinical tool that estimate individualized recurrence risks with and without adjuvant anti-PD1 therapy, quantifies the absolute benefit of treatment for pts with high-risk resected melanoma, facilitating personalized adjuvant therapy decisions.
Anti–PD-1 (PD-1) monotherapy versus combination with anti–CTLA-4 for metastatic uveal melanoma (MUM) patients (pts).
Silva, Ines Esteves Domingues Pires da, Grynberg, Shirly , Forschner, Andrea , Vincent, T., Liddle, Conner, Hopkins, Sam , Steinkerchner, Megan, Khaddour, Karam , Huerta, Luis Paul Del Carpio, Win, Su, Gebhardt, Christoffer , Hans, Tasvinder Kaur, Carlino, M S, Block, Matthew S. , Menzies, A, LO, S, Long, Georgina V., Long, Georgina V. , Lo, Serigne , Long, Georgina V , Lo, Serigne N , Grynberg, Shirly , Stoff, Ronen , Ma, Vincent The-Luc , Steinkerchner, Megan S. , Weichenthal, Michael , Carpio, L.P. del , Boutros, Andrea , Carlino, Matteo S. , Menzies, Alexander M

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 9535-9535

10.1200/jco.2026.44.16_suppl.9535 Get It

9535 Background: MUM carries a poor prognosis with few effective treatments, especially for HLA-A*02:01-negative pts. While a subset of MUM pts responds to immune checkpoint inhibitors, the comparative efficacy of IPI+PD1 versus PD1 monotherapy is unclear. This study compares objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety between these regimens in MUM. Methods: MUM pts treated with PD1 or IPI+PD1 at 15 major melanoma centres (from Australia, Europe, United States and Israel) were included. Demographics, patient and disease characteristics, and clinical outcomes were examined. Univariate and multivariate (MVA) analyses were performed to identify clinical predictors of response and survival. Results: Of 412 MUM pts treated, 150 (36%) had PD1 and 262 (64%) received PD1+IPI. Compared to the PD1 group, PD1+IPI-treated pts were younger (64 vs. 70 years; p<0.001), had higher rate of elevated LDH (44% vs. 31%; p=0.037), and more frequently had prior treatment with tebentafusp (6.5% vs. 1.3%; p=0.031). Median follow-up from commencement of PD1+/-IPI was 4.9 years (95% CI 4.7 – 6.1). ORR was higher in IPI+PD1 group (18%) vs. PD1 (9%) (p=0.008), particularly in males (p=0.009), patients with liver metastases (p=0.018) and with lung metastases (p=0.011), with elevated LDH (p=0.047) and with no prior treatment with tebentafusp (p=0.007). PFS and OS at 1 and 2 years were numerically higher with IPI+PD1 (1- and 2-year PFS: 23% and 15%; 1- and 2-year OS: 63% and 39%) vs. PD1 (1- and 2-year PFS: 17% and 11%; 1- and 2-year OS: 54% and 36%), but these differences were not statistically significant (p>0.05). On MVA, adjusting for predefined variables (age, gender, ECOG PS, LDH, presence/absence of liver/lung metastases, prior treatment with tebentafusp), IPI+PD1 was associated with higher ORR (OR 2.71, 1.30 – 6.05; p=0.01) but not with PFS or OS compared to PD1. Presence of liver metastases (ORR [OR 0.28; 95% CI 0.13 - 0.64], PFS [HR 1.61; 95% CI 1.11 - 2.34], OS [HR 2.02; 95% CI 1.32 - 3.10]), ECOG PS≥2 (PFS [HR 1.82; 95% CI 1.07 - 3.10], OS [HR 2.24; 95% CI 1.25-4.01]), elevated LDH (PFS [HR 1.66; 95% CI 1.30 - 2.11], OS [HR 2.39; 95% CI 1.84-3.10]) and prior tebentafusp treatment (OS [HR 2.36; 95% CI 1.21-4.59]) were also independent predictors of response and/or survival. A higher percentage of pts experienced grade ≥3 immune-related adverse events (irAEs) in the IPI+PD1 group compared to the PD1 group (34% vs 13%, p<0.0001). Most pts ceased treatment due to progression (234, 57%), and more pts stopped due to toxicity in the IPI+PD1 vs. PD1 group (25% vs. 9%, p<0.0001). Conclusions: In pts with MUM, IPI+PD1 demonstrated a higher ORR but did not improve survival compared with PD1 alone. IPI+PD1 was more toxic, leading to early treatment discontinuation in one-quarter of pts. These findings may help guide treatment selection in MUM.
Phase 3 randomized trial to evaluate the impact of anselamimab on all-cause mortality in κ light-chain amyloidosis.
Wechalekar, Ashutosh D., Dispenzieri, Angela, Sanchorawala, Vaishali, Kastritis, E K, Zepeda, Victor H. Jimenez-, Suzuki, Kenshi, Lentzsch, Suzanne , Huart, Antoine , Carpinteiro, Alexander , Swenson, Eugene , Khan, Zilehuma, Catini, Julia, Kulkarni, Hrishikesh, Meltzer, Brian Adam, Mercuri, Michele, Lake, Stephen, Liedtke, Michaela , Investigators, On Behalf of the Pittsburgh Post Cardiac Arrest Service, Wechalekar, Ashutosh D. , Dispenzieri, Angela , Sanchorawala, Vaishali , Bhutani, Divaya , Bianchi, Giada , Suzuki, Kenshi , Khan, Zilehuma, Kulkarni, Hrishikesh, Lake, Stephen

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7501-7501

10.1200/jco.2026.44.16_suppl.7501 Get It

7501 Background: AL amyloidosis is a plasma cell dyscrasia (PCD) characterized by κ or λ Ig light chain amyloid fibrils that deposit in vital organs. Anselamimab is an investigational mAb designed to complement anti-PCD therapy through accelerated removal of amyloid fibrils. Cardiac Amyloid Reaching for Extended Survival (CARES) studies (NCT04512235 and NCT04504825) investigated the efficacy and safety of anselamimab compared with placebo, in addition to anti-PCD therapy. Methods: Alongside anti-PCD therapy with CyBorD (daratumumab was permitted) newly diagnosed patients with European modification of Mayo stage IIIa or IIIb AL amyloidosis were randomized 2:1 to receive anselamimab (1000 mg/m 2 ) or placebo (normal saline) IV every 7 days for 4 weeks followed by every 14 days for the remainder of the blinded study (18 months after the last participant enrolled). The primary endpoint was a hierarchical combination of time to all-cause mortality (ACM) and frequency of adjudicated cardiovascular hospitalizations (CVH) using the Finkelstein-Schoenfeld test and win-ratio in the combined study population. Subgroup analysis by involved κ or λ free light chain (iFLC) was prespecified. Results: 271 patients were randomized to receive anselamimab and 135 placebo. Baseline characteristics were similar between treatment arms. The median duration of treatment was 21.4 months and 21.1 in the anselamimab and placebo arms, respectively. Daratumumab was used in 79.3% and 83.7% of the anselamimab and placebo arms, respectively. Results of the primary efficacy analyses are shown in the table. Anselamimab-treated patients with κ iFLC had a 62% reduction in ACM (HR = 0.38; 95% CI, 0.17, 0.86; nominal P = 0.012) and a 71% reduction in risk for CVH (estimated CVH rate ratio = 0.29; 95% CI, 0.10, 0.87; nominal P = 0.028). Patients with λ iFLC had a 10% reduction in risk for CVH; none in ACM. Safety data were comparable between both treatment arms. In anselamimab-treated patients, safety findings were similar between κ subgroup and full population. Conclusions: Anselamimab, a κ light chain–directed anti-fibril monoclonal antibody used alongside standard of care chemotherapy, offers a first-in-class, new therapeutic option for patients with newly diagnosed κ AL amyloidosis. Clinical trial information: NCT04512235 and NCT04504825 . Summary of primary efficacy endpoints. Endpoint Overall κ Isotype λ Isotype Anselamimab (N=271) Placebo (N=135) P -value Anselamimab (N=48) Placebo (N=24) P -value Anselamimab (N=219) Placebo (N=109) P -value ACM and CVH win ratio (95% CI) 1.1 (0.8, 1.5) 0.332 2.06 (0.98, 4.31) 0.100 0.9 (0.6, 1.3) 0.848 ACM n (%) 90 (33.2) 52 (38.5) 15 (31.3) 14 (58.3) 73 (33.3) 37 (33.9) HR (95% CI) 0.8 (0.6, 1.1) 0.290 0.38 (0.2, 0.9) 0.012 1.0 (0.7, 1.5) 0.647 CVH Frequency/year (95% CI) 0.6 (0.4, 0.8) 0.9 (0.6, 1.4) 0.145 0.41 (0.2, 0.8) 1.4 (0.6, 3.4) 0.028 0.7 (0.4, 1.0) 0.8 (0.4, 1.3) 0.664 Incidence risk ratio (95% CI) 0.7 (0.4, 1.2) 0.29 (0.1, 0.9) 0.9 (0.5, 1.7)
Long-term safety outcomes of pregnancy among young breast cancer survivors: Results from a prospective, multicenter cohort study.
Zheng, Yue, Niman, Samuel M. , Dibble, Kate, Rosenberg, Shoshana M., Ruddy, Kathryn Jean, Gelber, Shari , Tamimi, Rulla, Peppercorn, Jeffrey , Schapira, Lidia, Come, Steven E. , Warner, Ellen, Lambertini, Matteo, Ginsburg, E, Partridge, Ann H., Sorouri, Kimia , Dibble, Kate E. , Rosenberg, Shoshana M. , Kirkner, Gregory J. , Ruddy, Kathryn J. , Tamimi, Rulla, Schapira, Lidia , Borges, Virginia F. , Warner, Ellen , Lambertini, Matteo , Ginsburg, Elizabeth S. , Partridge, Ann H.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 632-632

10.1200/jco.2026.44.16_suppl.632 Get It

632 Background: Prospective data on the risk of breast cancer (BC) recurrence among young BC survivors who have a subsequent pregnancy are limited. We sought to evaluate the long-term impact of pregnancy and live birth on BC outcomes in the Young Women’s Breast Cancer Study (NCT01468246), a prospective multicenter study of women aged ≤40 years at BC diagnosis. Methods: Women with stage 0-III BC without prior hysterectomy were included. The primary endpoint was breast cancer-free interval (BCFI) between patients with and without a (a) pregnancy and (b) live birth after BC. Secondary endpoints were distant recurrence-free interval (DRFI) and overall survival (OS). A time-varying Cox proportional hazards model was performed by estrogen receptor (ER) status, controlling for age at diagnosis, tumor stage, HER2 status, tumor grade, parity at diagnosis, and germline pathogenic variant status. Results: Among 1,016 BC survivors at a median follow-up of 12 (range, 0.5-18.5) years, 198 reported ≥1 pregnancy and 165 reported ≥1 live birth post-diagnosis. Among survivors who reported a post-diagnosis pregnancy, median age at diagnosis was 32 (range, 17-40) years; most had stage I (35%) or II (40%) BC, with 72% hormone receptor (HR)-positive and 25% HER2+; 42% were nulligravid and 60% were nulliparous at diagnosis. Among BC survivors who did not become pregnant post-diagnosis, median age at diagnosis was 37 (range, 21-40) years; most had stage I (35%) or II (43%) BC, with 75% HR-positive and 28% HER2+; 25% were nulligravid and 29% were nulliparous at diagnosis. Among BC survivors with ER-positive tumors (n = 737), pregnancy after BC was not associated with a difference in BCFI (adjusted hazard ratio [HR] 0.60, 95% CI 0.31-1.16, P = 0.130), DRFI (HR 0.73, 95% CI 0.35-1.55, P = 0.416), or OS (HR 0.58, 95% CI 0.24-1.40, P = 0.227). Similarly, live birth after BC did not impact BCFI (HR 0.83, 95% CI 0.45-1.55, P = 0.560), DRFI (HR 1.04, 95% CI 0.52-2.06, P = 0.923), or OS (HR 0.77, 95% CI 0.34-1.76, P = 0.541). Outcomes among BC survivors with ER-negative tumors (n = 278) were also not affected by post-diagnosis pregnancy (BCFI [HR 1.48, 95% CI 0.70-3.14, P = 0.304], DRFI [HR 1.59, 95% CI 0.68-3.75, P = 0.287], OS [HR 0.99, 95% CI 0.39-2.49, P = 0.975]) or live birth (BCFI [HR 1.02, 95% CI 0.41-2.53, P = 0.974], DRFI [HR 0.80, 95% CI 0.24-2.69, P = 0.722], OS [HR 0.39, 95% CI 0.09-1.69, P = 0.208]). Conclusions: In this multicenter, prospective study with 12 years of median follow-up, pregnancy and live birth after BC did not impact BC events or overall survival, irrespective of ER status. These long-term data from a modern cohort provide reassurance for young BC patients interested in future fertility. Clinical trial information: NCT01468246 .
EA1181: Accuracy of pre-surgery MRI to predict pathologic complete response after taxane, trastuzumab, and pertuzumab (THP) in HER2-positive breast cancer.
Tung, NM, Zhao, Fengmin, Partridge, Savannah C., Wright, Jean, Recht, Abram, Weiss, Anna, Tjoe, Judy A., Feldman, Sheldon M. , Smith, Mary Lou , O'Sullivan, Ciara Catherine, Sardesai, Sagar D., Winer, Eric P., Partridge, Ann H., Carey, L, DeMichele, Angela, Tung, Nadine , Zhao, Fengmin , Partridge, Savannah C , Recht, Abram , Weiss, Anna, Tjoe, Judy A., Rocque, Gabrielle B. , O’Sullivan, Ciara C. , Sardesai, Sagar , Badve, Sunil , Winer, Eric P. , Miller, Kathy D. , Partridge, Ann H. , Carey, Lisa A. , Rahbar, Habib , DeMichele, Angela , Wolff, Antonio C.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 603-603

10.1200/jco.2026.44.16_suppl.603 Get It

603 Background: Accurate prediction of pathologic complete response (pCR) after preoperative therapy for HER2-positive (HER2+) breast cancer can help triage patients to immediate surgery vs additional preoperative therapy. Pre-surgery (i.e., after neoadjuvant therapy) imaging studies may help estimate the likelihood of pCR. In EA1181, patients (pts) with stage II-IIIA HER2+ breast cancer received four cycles of preoperative taxane, trastuzumab, and pertuzumab (THP×4). Pre-surgery imaging was required, though the specific imaging modality was not mandated. Here, we report the accuracy of pre-surgery breast MRI to predict pCR (ypT0/Tis, ypN0). Methods: Among 2,141 pts treated with THPx4, 1,378 had pre-surgery breast MRI and were representative of the overall cohort, although T3 tumors were more common (16% vs 9%). MRI reports were available for 1,351 pts; all reports were centrally reviewed and classified as radiologic complete response (rCR; no residual tumor enhancement and normalization of lymph nodes, if applicable) or radiologic residual disease (rRD). Reports with indeterminate radiologic response were independently reviewed by two study radiologists blinded to pathology outcomes. Among pts with rCR who had pathologic residual disease (pRD), we also assessed the extent of residual disease by residual cancer burden (RCB) score. Among pts with rRD who had a pCR, we determined the proportion who only had residual ductal carcinoma in situ (DCIS). Results: See Table. Conclusions: After neoadjuvant therapy, preoperative MRI accurately predicted pCR in 86% of patients with HER2+/ER− disease and may help identify patients who can proceed directly to surgery. MRI is insufficient to predict pCR for pts with HER2+/ER+ disease, as only 55% with complete response on MRI had a pCR at surgery. A pre-surgery MRI that indicated residual disease was accurate in 80% of pts with HER2+/ER+ disease, but in only 45% of pts with HER2+/ER- cancer. Accurately predicting residual disease after THPx4 allows for consideration of additional therapy that may increase the chance of pCR. Combining imaging like MRI with other biomarkers, such as tissue-based markers or circulating tumor DNA, may improve prediction of pCR and facilitate personalization of treatment decisions in HER2+ breast cancer. All pts with pre-surgery MRI (n=1351)pCR rate overall in this cohort = 47% MRI result Pathology pCR pRD rCR 70.6% (341/483) 29.4%(142/483) 78% had RCB1 rRD 34%(295/868) 21% of 295 had DCIS only 66.01% (573/868) ER- (n=589)*Overall pCR rate in ER- subset = 68% MRI result Pathology pCR pRD rCR 86.1% (205/238) 13.9% (33/238) 85% had RCB1 rRD 55.3% (194/351) 19% of 194 had only DCIS 44.7% (157/351) ER+ (n= 762)*Overall pCR rate in ER+ subset = 31% MRI result Pathology pCR pRD rCR 55.5% (136/245) 44.5% (109/245) 76% had RCB1 rRD 19.5% (101/517) 26% of 101 had only DCIS 80.5% (416/517)
Organ- and histology-specific molecular and immune landscape of metastatic breast cancer.
Deshmukh, Sachin Kumar, Fanucci, K., Oesterreich, Steffi, Wu, Sharon, Xiu, Joanne, Advani, Pooja , Coelho, P. Barreto, Schnitt, S J, Lin, Nancy, Tolaney, Sara M., Metzger, Otto, Sledge, George W., Jeselsohn, Rinath, Marta, Guilherme Nader , Deshmukh, Sachin Kumar , Lee, Adrian V. , Oesterreich, Steffi , Wu, Sharon , Xiu, Joanne , Coelho, Priscila Barreto, Lustberg, Maryam B. , Tolaney, Sara M. , Mayer, Erica L. , Metzger, Otto , Jeselsohn, Rinath

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 1024-1024

10.1200/jco.2026.44.16_suppl.1024 Get It

1024 Background: Invasive lobular carcinoma (ILC) is a distinct breast cancer (BC) subtype with dissemination patterns differing from invasive breast carcinoma of no special type (IBC-NST). While genomic differences between ILC and IBC-NST have been described, the extent to which molecular and immune profiles vary by metastatic organ and histology is poorly characterized. Methods: We conducted a retrospective analysis to evaluate organ- and histology-specific molecular features of metastatic BC (mBC). Patients with metastatic IBC-NST or pure ILC underwent NGS (592, NextSeq; WES/WTS, NovaSeq; Caris Life Sciences). Tumor mutational burden (high ≥10 mut/Mb), PD-L1 expression (22C3), and immune cell fractions (RNAseq deconvolution, quanTIseq) were assessed. Analyses were restricted to sites with ≥10 biopsies per histology. Comparisons used chi-square or Mann–Whitney U tests with multiple testing correction (q < 0.05). Results: A total of 2645 mBC biopsies (605 ILC; 2040 IBC-NST) were analyzed (Table). In ILC, ERBB2 mut frequency differed by metastatic site (q<0.01), with higher prevalence in liver (32.7%) and lower in gastrointestinal (GI) lesions (3.7%). In IBC-NST, ESR1 and GATA3 mut and FGFR1 amplification were enriched in liver metastases, whereas PD-L1 expression was highest in skin (20.7%) and lowest in liver (5.0%). No organ-specific differences were observed for PIK3CA, AKT, PTEN, BRCA1/2 or RB1 . Across metastatic sites, both ILC and IBC-NST showed differences in B cells, macrophages (M1/M2), neutrophils, NK cells, dendritic cells, CD8+ T cells, and Tregs (all q < 0.05); CD4+ T-cell differences were observed only in IBC-NST (q = 0.002). In organ-specific ILC vs IBC-NST comparisons, CDH1 mut were more frequent in ILC across sites, along with higher PIK3CA mut in skin (ILC 51.3% vs IBC-NST 34.4%) and higher ERBB2 mut in liver (32.7% vs 3.3%), whereas a higher TP53 mut frequency was observed in IBC-NST in skin (28.5% vs 52.3%) and lymph nodes (LND) (23.5% vs 55.5%) (all q < 0.01). Conclusions: mBC exhibits marked organ-specific molecular and immune heterogeneity that differs by histology. These findings support histology- and site-aware interpretation of metastatic biopsies and may inform biomarker assessment and treatment decisions in advanced disease. BC-NST ILC Skin LND Bone Breast Liver Perit. CNS q-value Skin LND Bone Breast GI Liver GYN Perit. CNS q-value N (specimens) 785 401 109 361 220 15 44 - 172 84 62 56 56 54 43 37 11 - ERBB2 mut (%) 3.2 3.1 3.2 2.3 3.3 7.1 2.5 1.0 7.1 7.4 16.4 15.4 3.7 32.7 2.4 5.7 11.1 <0.01 ESR1 mut (%) 9.4 5.2 8.3 16.0 28.2 7.1 2.4 0.0 7.8 7.2 8.9 9.8 16.7 26.0 4.9 20.0 0.0 0.9 FGFR1 amp (%) 10.1 6.6 5.6 12.8 16.5 0.0 9.7 0.02 4.4 3.4 6.7 6.1 2.4 5.6 7.7 18.5 0.0 1.0 IHC-PD-L1 (%) 20.7 - 5.3 16.0 5.0 11.1 10.3 0.02 8.9 - 5.0 5.7 6.1 0.0 0.0 0.0 14.3 1.0 TMB-High (%) 10.7 10.1 8.8 8.8 8.5 14.3 21.4 0.8 27.6 11.0 19.6 28.0 11.3 19.6 9.8 32.4 22.2 0.8 Perit: peritoneum; CNS: central nervous system; GYN: genital tract.
Crisis-related self-reported symptoms of posttraumatic stress disorder in graduate medical education trainees: results from a multi-institutional study
Akhtar, Saadia, West, Colin P. , Satele, Daniel , He, Celestine , Thomas, Larissa R. , Sliwka, Diane, Julian, Katherine A. , Leitman, I Michael, Ripp, Jonathan, Satele, Daniel V, West, C P , Akhtar, Saadia R. , Sliwka, Diane, Dyrbye, Liselotte N. , Ripp, Jonathan

Academic Medicine | May 25, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1093/acamed/wvag157 | PMID 42179175 Get It

Abstract Purpose Crisis periods—defined as sustained disruptions to the clinical environment resulting in increased workload, exposure to high-acuity patient care, or limited access to coping resources—can lead to posttraumatic stress disorder (PTSD) among residents and fellows (trainees). By examining self-reported pandemic-related PTSD symptoms, associated risk factors, and their consequences, this study aims to identify vulnerable groups and inform institutional strategies to support trainee well-being during and after crisis events. Method A multi-institutional cross-sectional survey was conducted at 3 U.S. academic medical centers between April and May 2022. Measures included the Primary Care PTSD Screen for DSM-5 (range 0 to 5, scores ≥4 indicate probable PTSD), 4-item PROMIS Social Isolation scale (normed T-score range 0 to 100 scale with higher scores indicating greater isolation), items exploring intent to stay at one’s institution, and demographics. Multivariable analysis adjusted for demographics, specialty, and postgraduate year. Results Of 6,057 eligible trainees, 3,185 (53%) participated in the survey, with 3,109 completing the PTSD screening. A total of 190 (6%) trainees screened positive for self-reported PTSD symptoms. Multivariable analysis revealed that female trainees had a higher odds of screening positive for self-reported PTSD symptoms compared to males (odds ratio [OR] 1.45; 95% confidence interval [CI], 1.03-2.04; P = .03). Greater social isolation was independently associated with increased PTSD risk (OR 1.09; 95% CI, 1.07-1.11; P &lt; .001). Additionally, trainees who did not intend to remain at their institution after training were more likely to screen positive for PTSD (OR 1.74; 95% CI, 1.17-2.58; P = .01). Conclusions Female gender, greater social isolation, and reduced intention to remain at one’s institution are independently associated with self-reported PTSD symptoms in trainees. Recognizing these relationships may enable health care leaders to proactively identify trainees at higher risk during crisis periods and to implement targeted, evidence-based interventions that promote well-being and workforce retention.
Outcomes and treatment patterns in germline BRCA1/2 carriers from two matched cohort studies
Morganti, Stefania , Kim, Se Eun , Jin, Qingchun , Cha, Jaeyoon , Zeigler, Jacqueline E, Newman, Alexandra Bili, Kirkner, Gregory J. , Snow, Craig , Zheng, Yue, Vincuilla, Julie, Parker, Tonia , Buehler, Ryan M. , Bychkovsky, Brittany L , Dibble, Kate E. , Sella, Tal , Ruddy, Kathryn J, Rosenberg, Shoshana M, Collins, Laura C. , Peppercorn, Jeffrey, Schapira, Lidia, Guzman-Arocho, Yaileen D, Come, Steven E. , Warner, Ellen, Poorvu, Philip D. , Lambertini, Matteo, Curigliano, G, Hughes, Melissa E. , Mittendorf, Elizabeth A, King, Tari A, Lin, Nancy U, Garber, Judy E, Tayob, Nabihah, Tolaney, S M, Partridge, Ann H, Zheng, Yue , Newman, Alexandra B , Zheng, Yue , Ruddy, Kathryn J , Peppercorn, Jeffrey M , Borges, Virginia F , Guzman-Arocho, Yaileen D , Come, Steven , Poorvu, Philip D , Lambertini, Matteo , Curigliano, Giuseppe , Mittendorf, EA , King, Tari A , Lin, Nancy U , Garber, J. E. , Tayob, Nabihah , Tolaney, Sara , Partridge, Ann H , Lynce, Filipa , Kirkner, Gregory , Snow, Craig , Vincuilla, Julie, Ruddy, Kathryn J. , Rosenberg, Shoshana M. , Peppercorn, Jeffrey , Schapira, Lidia , Borges, Virginia F. , Guzmán‐Arocho, Yaileen D. , Warner, Ellen , Lambertini, Matteo , Curigliano, Giuseppe , King, Tari A. , Lin, Nancy U. , Garber, Judy E. , Partridge, Ann H.

JNCI Cancer Spectrum | May 23, 2026 | Volume: 10 | Issue: 4 | Pages: No page available

10.1093/jncics/pkag055 | PMID 42185079 Get It

Abstract Background Whether outcomes of germline BRCA1/2 (gBRCA1/2)-associated breast cancer differ compared with sporadic tumors is controversial. We explored the impact of gBRCA1/2 pathogenic variant (PV) status beyond established prognostic features. Methods We conducted 2 retrospective, matched cohort studies comparing gBRCA1/2 PV carriers and noncarriers with HER2-negative, stage I-III breast cancer (Clinical Outcomes Quality Database [COQD] cohort: 185 carriers, 555 noncarriers; Young Women’s Breast Cancer Study [YWS] cohort: 113 carriers, 226 noncarriers). Matching factors were age, stage, hormone receptor status, and year of diagnosis. Clinicopathological features, treatments, and survival outcomes were compared between carriers and noncarriers. Results Most patients in COQD had stage I-II disease (87.2%), and more carriers than noncarriers had genetic testing before diagnosis (33% vs 5.6%, P &lt; .001). In YWS, 22.7% of patients had stage III tumors, and few were tested before diagnosis (14.8% of carriers vs 1.7% of noncarriers; P &lt; .001). Carriers in COQD received chemotherapy more often than noncarriers (81.1 vs 67.0%, P &lt; .001), including platinum (P = .010); the proportion was similar for carriers and noncarriers in YWS. After adjusting for chemotherapy, relapse-free survival was longer in carriers than noncarriers in COQD (adjusted hazard ratio = 0.48 [95% CI = 0.26 to 0.87], P = .016), and a favorable trend was observed for other survival outcomes in both cohorts. Triple-negative tumors appeared to drive the differences. Conclusions We observed a trend toward improved outcomes in gBRCA1/2 PV carriers compared with noncarriers. These findings suggest that carriers should not receive more aggressive treatment solely based on their germline mutation status. Prospective clinical trials in this population are warranted.
Designing the Thinking: Reimaging Health Informatics via Journey Maps and Personas
Joseph, Amanda L. , Price, Amy , Petersen, Carolyn , Quintana, Yuri , Petersen, Carolyn

Studies in Health Technology and Informatics | May 21, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.3233/shti260610 | PMID 42175279 Get It

Personas and patient journey maps are poised to improve human-centered care delivery, and technology design. However, they remain largely underutilized in healthcare settings globally. A persona composite and a journey map inspired by narratives of medical students managing illness in addition to the rigors of academia is presented. This scoping review illustrates how journey mapping and personas are used in healthcare contexts to frame the experiences of patients; formal and informal caregivers; nurses; and physicians. The heterogeneous findings reveal that despite their promise the utility of these tools is largely unexplored in health informatics.
Temporal relationship between hematoma resolution and functional recovery after middle meningeal artery embolization for chronic subdural hematoma
DeMessie, Bluyé , Essibayi, Muhammed Amir, Karandish, Alireza, Park, Jaewoo , Haranhalli, Neil, Baker, Amanda, Zampolin, R, Brook, A, Lee, S, Adeeb, Nimer, Li, Yan-Lin, Ortega, Diego Alejandro, Cancelliere, N, Diestro, Jose Danilo, Carnevale, Joseph A., Schreiber, Craig , Abecassis, Zachary, Raub, Spencer, Sioutas, Georgios S. , Kvint, Svetlana , Falzon, Andrew, Cantrell, Vance, Holliday, Brian, Maleknia, Pedram D., Cruz-Criollo, Leonardo, Schimmel, Samantha, Musmar, Basel, Alexander, Matthew D. , Zermeno, Jorge Rios, Koul, Prateeka , Aljuboori, Ahmed , Vollherbst, D, Cooper, J , Ogilvy, Christopher S., Al-Mufti, Fawaz, Möhlenbruch, Markus A., Scarcia, Luca, Schirmer, Clemens M., Huynh, Thien, Settecase, Fabio , Tjoumakaris, Stavropoula, Jabbour, Pascal, Vakharia, Kunal, Zanaty, Mario, Ortega-Gutierrez, Santiago, Jones, J, Nasser, Hussein H., Sundararajan, Sri Hari , Mosimann, Pascal J., Nossek, Erez , Raz, Eytan, Kasab, S Al, Spiotta, Alejandro M., Michelozzi, Caterina , Saraceno, Davide , Srinivasan, Visish M., Burkhardt, Jan-Karl, Santini, Pietro Mario, Levitt, Michael R., Lanzino, Giuseppe, Brinjikji, Waleed, Knopman, Jared, Kass-Hout, T, Spears, Julian, Marotta, Thomas, Pereira, Vitor Mendes, Fuschi, Maurizio , Dmytriw, Adam A., Altschul, David J., _, _, Kostynskyy, Alex , Goren, Oded , Oliver, Jeffrey Daniel, Milnerowicz, Małgorzata , Papaxanthos, Jean , Eker, Omer, Barreau, Xavier, Courret, Thomas , Berge, Jerome, Engelhardt, Julien , Diestro, Jose Danilo Bengzon , Li, Yan-Lin , Rios Zermeno, Jorge , Diestro, Jose Danilo B , Li, Yan-Lin , Essibayi, Muhammed Amir , Salim, Hamza , Karandish, Alireza , Khatri, Deepak , Haranhalli, Neil , Zampolin, Richard L. , Adeeb, Nimer , Simonato, Davide , Ortega-Moreno, Diego Alejandro , Cancelliere, Nicole M , Carnevale, Joseph Anthony , Orscelik, Atakan , Abecassis, Zachary A. , Raub, Spencer , Salsano, Giancarlo , Kasem, Rahim Abo , Falzon, Andrew , Abaricia, Jefferson O. , Maleknia, Pedram Daniel , Cruz‐Criollo, Leonardo , Schimmel, Samantha J. , Musmar, Basel , Gajski, Domagoj, Alwakaa, Omar , Ogilvy, Christopher S. , Al‐Mufti, Fawaz , Kalousek, Vladimir , Möhlenbruch, Markus , Scarcia, Luca , Schirmer, Clemens M. , Huynh, Thien , Tawk, Rabih G. , Tjoumakaris, Stavropoula , Jabbour, Pascal , Zanaty, Mario , Ortega-Gutierrez, Santiago , Jones, Jesse , Colasurdo, Marco , Nasser, Hussein, Mosimann, Pascal J , Raz, Eytan , Spiotta, Alejandro M , Castellan, Lucio , Sette, Bruno Del , Panni, Pietro , Srinivasan, Visish M. , Burkhardt, Jan‐Karl , Marnat, Gaultier , Levitt, Michael R. , Lanzino, Giuseppe , Brinjikji, Waleed , Knopman, Jared , Kass‐Hout, Tareq , Spears, Julian , Dmytriw, Adam A. , Altschul, David , Galecio‐Castillo, Milagros , Cespedes, Jorge , Oliver, Jeffrey , Eker, Omer , Barreau, Xavier , Berge, Jérôme , Jecko, Vincent

Journal of Neurosurgery | May 20, 2026 | Volume: No volume available | Issue: No issue available | Pages: 1-12

10.3171/2025.12.jns251884 | PMID 42172679 Get It

OBJECTIVE The objective was to evaluate the trajectories of hematoma resolution and functional improvement after middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH), model the temporal pattern of cSDH resolution, and identify factors associated with favorable outcomes. METHODS This real-world multicenter retrospective study included cSDH patients treated with MMAE at 24 centers between 2019 and 2024. Hematoma thickness was measured at baseline and at follow-up intervals (1–4 weeks, 1–3 months, 3–6 months, 6–12 months, and > 12 months after embolization). Resolution patterns were modeled using exponential decay functions. Modified Rankin Scale (mRS) scores assessed functional outcomes. Good functional outcome was defined as mRS score ≤ 2. Resolution patterns were modeled using exponential decay functions to estimate time to 50% and 80% reduction. Patients were categorized as complete resolution (≥ 99%) or by quartile of the remaining distribution (substantial [73%–98%], moderate [53%–73%], partial [27%–53%], minimal [< 27%]). The primary outcome was good functional status (mRS score ≤ 2). RESULTS The authors analyzed a total of 1781 patients with 2295 cSDHs who underwent MMAE. The mean ± SD age was 72.8 ± 12.4 years and 68.1% of patients were male. The initial mean hematoma thickness was 15.31 ± 6.53 mm, decreasing to 5.24 ± 5.91 mm at final follow-up (mean reduction 64.3% ± 42.1%). Resolution followed an exponential decay pattern, with an estimated time to 50% reduction of 1.8 months and to 80% reduction of 8.9 months. Complete resolution occurred in 1031 of 2224 patients (46.4%) with complete follow-up. The median (IQR) mRS score improved from 1 (0–3) at baseline to 0 (0–2) at > 12 months. Good functional outcomes were more common in patients with complete versus minimal resolution (68.9% vs 35.0%, p < 0.001). Achieving ≥ 73% resolution within 90 days was associated with better outcomes (good outcome in 76.9% of those with ≥ 73% resolution vs 67.3% in those without, p < 0.001). Neurological deterioration was the strongest predictor of lack of good outcome (23.7% in patients with neurological deterioration vs 82.4% without, p < 0.001). CONCLUSIONS After MMAE for cSDH, reduction in hematoma thickness follows a predictable exponential decay pattern. Greater extent (≥ 80%) and faster timing (within 90 days) of resolution are valuable prognostic indicators. Functional outcomes improve progressively through 6–12 months after the procedure. The relationship between resolution extent and functional outcomes provides quantitative benchmarks for evaluating treatment response.