Wen PY, Berry DA, Buxton MB
… +30 more, Colman H, de Groot J, Lim M, Mellinghoff I, Perry JR, Weller M, Blondin NA, Butt OH, Damek DM, de la Fuente MI, Drappatz J, Dunbar E, Giglio P, Hyddmark EV, Iwamoto F, Jaeckle KA, Kim L, Kling HM, Lee EQ, Mantica M, Mikkelsen T, Nabors B, Newton HB, Olson JJ, Schiff D, Walbert T, Weathers SP, Cloughesy T, Lassman AB, GBM AGILE Regorafenib Study Group
PURPOSE: Malignant ovarian germ cell tumors (MOGCTs) are rare, aggressive malignancies predominantly affecting young women. Unlike testicular germ cell tumors, prognostic factors are poorly understood, with small studies...PURPOSE: Malignant ovarian germ cell tumors (MOGCTs) are rare, aggressive malignancies predominantly affecting young women. Unlike testicular germ cell tumors, prognostic factors are poorly understood, with small studies suggesting advanced stage as an adverse factor. Here, we examine a large international series to identify relevant prognostic factors. METHODS: We analyzed data from 254 patients with International Federation of Gynecology and Obstetrics stage IC-IV MOGCT, requiring surgery and chemotherapy between 1971 and 2018 at two UK and the Multicenter Italian Trials in Ovarian Cancer centers. RESULTS: The median age was 27 years (IQR, 21-31). Initial treatment was surgery in 87.8% of patients (50.4% fertility sparing, 37.4% nonsparing) or neoadjuvant chemotherapy. Most underwent BEP or POMB/ACE chemotherapy, with 32.5% receiving high-dose chemotherapy (HDCT) at relapse. First-line treatment resulted in a complete response in 84.6% (n = 215) and partial response or stable disease in 7.9% (n = 20), while 4.7% (n = 12) progressed. Overall, 37 patients (14.6%) died of disease. Ten-year progression-free survival and cancer-specific survival (CSS) was 82.8% (95% CI, 77.2 to 87.2) and 83.2% (95% CI, 77.3 to 87.7), respectively. CSS for stage IV disease was 79.4% (95% CI, 69.5 to 86.4). Age ≥35 years (hazard ratio [HR], 2.8 [95% CI, 1.5 to 5.4]; = .003), stage III/IV disease (HR, 1.4 [95% CI, 1,0.2 to 1.9]; = .035), and nondysgerminoma histology (HR, 7.3 [95% CI, 1.9 to 64.8]; = .01) had worse CSS on multivariable analysis. By contrast, CSS of immature grade 2/3 MOGCT mirrored dysgerminomas. HDCT appeared to improve survival in first but not later relapses. CONCLUSION: Advanced stage (III/IV), age >35 years, and nondysgerminoma (excluding grade 2/3 immature teratomas) are adverse prognostic factors. Stage IV disease can achieve 80% long-term survival rates, and HDCT improves survival in first but not second relapse.
Nie RC, Jin Y, Liang CC
… +24 more, Li YF, Chen YB, Sun XW, Guan WL, Wang ZX, Qiu HB, Wang W, Chen S, Zhang DS, Ling YH, Xi SY, Cai MY, Chi J, Yang QX, Liu ZM, Guan YX, Chen YM, Li JB, Tang XW, Peng JS, Wang F, Zhou ZW, Xu RH, Yuan SQ
The NEOSUMMIT-01 trial previously showed that adding the PD-1 antibody toripalimab to perioperative chemotherapy improved the pathologic response in patients with locally advanced gastric or gastroesophageal junction can...The NEOSUMMIT-01 trial previously showed that adding the PD-1 antibody toripalimab to perioperative chemotherapy improved the pathologic response in patients with locally advanced gastric or gastroesophageal junction cancer. Here, we present the event-free survival (EFS) and overall survival (OS) after extended follow-up. A total of 108 patients were enrolled (toripalimab plus chemotherapy, n = 54; chemotherapy alone, n = 54). At the data cutoff date (August 29, 2025), the median follow-up was 43.2 months (interquartile range: 36.6-53.7). The 3-year EFS was 74.7% (95% CI, 63.6% to 87.7%) in the toripalimab plus chemotherapy group and 56.2% (95% CI, 43.3% to 73.0%) in the chemotherapy group, with a hazard ratio (HR) of 0.51 (95% CI, 0.27 to 0.98; = .044). The 3-year OS was 81.3% (95% CI, 71.4% to 92.4%) versus 72.2% (95% CI, 61.2% to 85.2%), respectively, with an HR of 0.45 (95% CI, 0.21 to 0.95; = .036). The survival benefits were consistent across most predefined subgroups and were maintained in the analysis excluding patients with dMMR. In conclusion, perioperative toripalimab plus chemotherapy significantly improved 3-year EFS and OS compared with chemotherapy alone, suggesting it as a promising treatment option for patients with locally advanced gastric or gastroesophageal junction cancer.
PURPOSE: Neoadjuvant immune checkpoint inhibition has shown promise in localized deficient mismatch repair (dMMR) colorectal cancer, yet the optimal treatment duration, regimen, and methods for response evaluation remain...PURPOSE: Neoadjuvant immune checkpoint inhibition has shown promise in localized deficient mismatch repair (dMMR) colorectal cancer, yet the optimal treatment duration, regimen, and methods for response evaluation remain undefined. This trial aimed to investigate the efficacy and safety of neoadjuvant pembrolizumab for patients with localized dMMR colon cancer. METHODS: Participants received a single cycle of pembrolizumab (4 mg/kg, max 400 mg, every-6-weeks dosing regimen), followed by a preoperative endoscopy with biopsies and surgery 3-5 weeks later. The primary end point was pathologic complete response (pCR); secondary and exploratory end points included major pathologic response (MPR), safety, survival, and endoscopic response assessment. RESULTS: From February 2023 to March 2024, 85 patients (median age 74 years) were enrolled. All received pembrolizumab; one patient declined surgery. Among 84 patients, pCR was achieved in 44% (37 of 84; 95% CI, 33 to 55), and MPR in 57% (48 of 84; 95% CI, 46 to 68). Two (2%) patients died of complications within 30 days of surgery. At a median follow-up of 18.4 months (IQR, 16.3-21.1), one patient had a recurrence, resulting in overall and disease-free survival rates of 98% and 96%. Grade 3 adverse events occurred in 11% of patients (9 of 85; 95% CI, 3 to 16), with three treatment-related events. In 81 patients, the sensitivity, specificity, and accuracy of the biopsies for predicting pCR were 68%, 75%, and 72%, respectively. In 76 patients, the sensitivity, specificity, and accuracy of the endoscopic images for predicting pCR were 77%, 93%, and 86%, respectively. CONCLUSION: A single cycle of neoadjuvant pembrolizumab led to pCR in nearly half of patients undergoing surgery for localized dMMR colon cancer. The utility of endoscopic evaluation may inform future strategies for patient selection in nonoperative management pathways.
Willmann J, Dee EC, Hendriks LEL
… +20 more, Dimitriou NM, Jongbloed M, Schoenfeld AJ, Drilon A, Ganesh K, Zhang YH, Feldman J, Werner R, Opitz I, Carrot-Zhang J, Schultz N, Veeraraghavan H, Jones DR, Awad M, Rudin CM, Popat S, De Ruysscher D, Gomez DR, Guckenberger M, Iyengar P
Advances in systemic therapy have improved outcomes for metastatic non-small cell lung cancer (NSCLC), yet resistance and progression remain nearly universal. Local therapies such as radiotherapy, surgery, and image-guid...Advances in systemic therapy have improved outcomes for metastatic non-small cell lung cancer (NSCLC), yet resistance and progression remain nearly universal. Local therapies such as radiotherapy, surgery, and image-guided ablation can extend disease control in selected patients, but existing classifications-including dynamic models of oligometastatic disease-assign a single state per patient and do not capture lesion-level heterogeneity. We introduce the concept of -the spatiotemporal dynamics of response and progression across lesions, organs, and patients-as a framework to characterize intrapatient heterogeneity and inform adaptive treatment strategies. Dimensions of metastatic trajectories include the magnitude and homogeneity of response, mechanisms of resistance, organotropism, and the pattern, site, extent, and pace of progression. This framework shifts the focus from overall disease states to individual lesion behavior over time, enabling strategies based on observed trajectories and strategies based on predicted ones. We review the biological foundations of intrapatient heterogeneity-including genomic diversification, nongenetic plasticity, and tumor-microenvironmental adaptation-that drive divergent lesion evolution and treatment response. Emerging biomarkers such as circulating tumor DNA and radiomic signatures, together with integrative genomic and functional imaging approaches, may allow tracking and prediction of trajectory evolution. Standardized reporting parameters are proposed to ensure consistent documentation and facilitate validation across studies. Integrating trajectory-based assessment into clinical practice could refine patient selection for local and systemic therapy, enable biology-informed adaptation of treatment timing and intensity, and provide a foundation for next-generation clinical trials aimed at precision management of metastatic NSCLC.
Sharma MR, Powderly J, Kuboki Y
… +23 more, Strickler JH, Perets R, Cohen JE, Raimbourg J, Nakajima TE, Yamamoto N, Cruz-Correa M, O'Neil B, Ghiringhelli F, Raghav K, Cecchini M, Bar J, Hunter Z, Burns M, Blaney M, Morrison-Thiele G, Aristide MN, Freise KJ, Li R, Li M, Vasilopoulos A, Biesdorf C, Sommerhalder D
PURPOSE: The antibody-drug conjugate Temab-A comprises the c-Met-targeting antibody telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload, adizutecan. A first-in-human phase I study (ClinicalTrials.gov id...PURPOSE: The antibody-drug conjugate Temab-A comprises the c-Met-targeting antibody telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload, adizutecan. A first-in-human phase I study (ClinicalTrials.gov identifier: NCT05029882) of Temab-A in patients with advanced solid tumors whose disease has progressed is currently ongoing. We report results from all patients in the dose escalation and the monotherapy metastatic colorectal cancer (mCRC) dose expansion. METHODS: Temab-A was administered intravenously once every 3 weeks as a monotherapy starting at 1.6 mg/kg in dose escalation. In mCRC dose expansion, patients with confirmed wild-type, microsatellite stable/mismatch repair-proficient mCRC were randomly assigned to 1.6 mg/kg, 2.4 mg/kg, or 3.0 mg/kg Temab-A once every 3 weeks. Primary end points included safety, pharmacokinetics, recommended phase II dose of Temab-A monotherapy, and Temab-A efficacy in patients with mCRC. RESULTS: In total, 57 patients received ≥1 dose of Temab-A in dose escalation; 3.0 mg/kg once every 3 weeks was established as the maximum tolerated dose. Collectively, in dose escalation and dose expansion, 122 patients with mCRC received Temab-A (dose escalation, N = 29; randomized dose optimization expansion, N = 93). All patients experienced ≥1 treatment-emergent adverse event; the most frequent were gastrointestinal (78%) and hematologic (71%) toxicities. Treatment-related discontinuations and deaths were infrequent (10% and 3%, respectively). Across all doses in patients with mCRC, overall response rate was 15.6% (95% CI, 9.6 to 23.2), disease control rate was 74.6% (95% CI, 65.9 to 82.0), and duration of response was 5.9 months (95% CI, 4.1 to 10.5); responses were more frequent at doses of 2.4 mg/kg and 3.0 mg/kg once every 3 weeks. Median progression-free survival was 4.6 months (95% CI: 4.0, 5.4), and median overall survival was 10.4 months (95% CI, 8.9 to 13.1). CONCLUSION: Temab-A at 2.4 mg/kg once every 3 weeks has a tolerable and manageable safety profile, with promising antitumor activity.
Cutler C, Kim HT, El Banna H
… +31 more, Halloran E, Matozel E, Ho VT, Koreth J, Gooptu M, Shapiro R, Kelkar A, Gibson C, Nikiforow S, Nageshwar P, Reynolds C, Ansuinelli M, Tamada R, Au C, Panaro K, Gervais C, DeFilipp Z, El-Jawahri A, Chen YB, El Jurdi N, Weisdorf D, Couriel D, Lee C, Arai S, Sahaf B, Bacigalupi J, Ji K, Soiffer R, Miklos D, Antin JH, Ritz J
PURPOSE: Chronic graft-versus-host disease (cGVHD) is a multisystem alloimmune disorder associated with abnormal B-cell biology and aberrant antibody responses. As B-cell-directed therapy can effectively treat establishe...PURPOSE: Chronic graft-versus-host disease (cGVHD) is a multisystem alloimmune disorder associated with abnormal B-cell biology and aberrant antibody responses. As B-cell-directed therapy can effectively treat established cGVHD, we tested whether prophylactic B-cell depletion could prevent the development of corticosteroid-requiring cGVHD following allogeneic transplantation. METHODS: We performed a randomized, placebo-controlled, and blinded trial comparing four doses of the B-cell-depleting antibody obinutuzumab (1,000 mg once on days 90, 180, 270, and 365 after transplantation) with placebo in transplant recipients receiving tacrolimus-based GVHD prevention at higher risk of cGVHD. The primary end point was the 1-year incidence of corticosteroid-requiring cGVHD. We measured antibody responses against Y chromosome-encoded minor histocompatibility (H-Y) antigens and correlated their occurrence with corticosteroid-requiring cGVHD incidence. RESULTS: One hundred seventy-eight participants were analyzed. The prophylactic administration of obinutuzumab resulted in profound B-cell depletion, a significant reduction in the incidence of steroid-requiring cGVHD at 1 year (13.3% 35.2%; = .0005), and an improvement in immunosuppression-free, relapse-free survival (48% 34% at 2 years; = .02). Neutropenia was more common in the obinutuzumab arm, but nonrelapse mortality was not different. In participants without preformed H-Y antibodies at the time of study intervention, obinutuzumab resulted in the most significant reduction in steroid-requiring cGVHD at 12 months (8.6%) compared with obinutuzumab participants with H-Y antibodies (40%) or placebo participants regardless of antibody status (41% with antibodies, 57% without antibodies). CONCLUSION: In allogeneic transplant recipients at higher risk of cGVHD, early B-cell depletion results in a significant reduction in the incidence of corticosteroid-requiring cGVHD.
PURPOSE: Mutations in , detected in over 20% of diffuse large B-cell lymphomas (DLBCLs), are associated with poor prognosis. However, clinical outcomes among patients with -mutant disease vary, with some patients showing...PURPOSE: Mutations in , detected in over 20% of diffuse large B-cell lymphomas (DLBCLs), are associated with poor prognosis. However, clinical outcomes among patients with -mutant disease vary, with some patients showing treatment responses similar to those with wild-type . This study aims to understand the clinical and molecular determinants underlying poor outcomes in -mutant DLBCL. METHODS: Clinical and molecular data for 3,091 patients were derived from 10 cohorts of patients with newly diagnosed DLBCL treated with frontline rituximab-based immunochemotherapy regimens. Targeted or whole-exome/whole-genome sequencing was available for all patients. Bulk RNA-seq was analyzed for 591 patient samples. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). RESULTS: mutant DLBCL differed from wild-type disease in pattern and number of genetic lesions, malignant B-cell expression states, and tumor microenvironment composition. mutations were 6-fold more prevalent than double-/triple-hit status, but conferred similar adverse prognostic risk. Among patients with -mutant disease, variant allele frequency (VAF) further stratified risk, with patients featuring VAF ≥ 75% (indicative of loss of heterozygosity) experiencing significantly inferior PFS/OS. Downregulation of interferon signaling and lower macrophage content were identified in -mutant samples derived from patients with poor outcomes or VAF ≥ 75%. mutations were adversely prognostic among patients with DLBCL assigned to specific LymphGen subtypes (EZB, MCD), malignant B-cell states (S1), and ecotypes (LE4, LE7, LE8), whereas outcomes were similar to wild-type disease within other molecular subtypes. In re-examination of the Phoenix trial data, addition of ibrutinib to R-CHOP improved PFS in patients with -mutant DLBCL and abrogated the deleterious impact of high VAF, irrespective of patients' age. CONCLUSION: The poor prognosis of -mutant DLBCL is dependent on intrinsic features, such as VAF, and modulated by co-occurring genomic lesions or lymphoma cell-intrinsic or microenvironmental expression patterns.
A medical student's first encounter with a hepatectomy comes full circle when he becomes a living liver donor for his wife with metastatic pancreatic cancer, reshaping his understanding of medicine as they navigate the u...A medical student's first encounter with a hepatectomy comes full circle when he becomes a living liver donor for his wife with metastatic pancreatic cancer, reshaping his understanding of medicine as they navigate the uncertainty of her diagnosis together.
Stepan L, Ansari S, Abramson JS
… +21 more, Okal A, Dell'Aringa J, Thompson EG, Crotta A, Chow VA, Kamdar M, Solomon SR, Johnston PB, Glass B, Mutsaers P, Arnason J, Mielke S, Shadman M, Hernandez-Ilizaliturri F, Izutsu K, Bachanova V, Ibrahimi S, Chabon JJ, Kurtz DM, Alizadeh AA, Peiser L
J Clin Oncol
· 2026 Jul · PMID 42044466
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Full text
We report correlative circulating tumor DNA (ctDNA) analyses from TRANSFORM (ClinicalTrials.gov identifier: NCT03575351) evaluating lisocabtagene maraleucel (liso-cel) versus standard of care (salvage immunochemotherapy,...We report correlative circulating tumor DNA (ctDNA) analyses from TRANSFORM (ClinicalTrials.gov identifier: NCT03575351) evaluating lisocabtagene maraleucel (liso-cel) versus standard of care (salvage immunochemotherapy, high-dose chemotherapy, autologous stem cell transplantation [ASCT]) in second-line large B-cell lymphoma (LBCL). ctDNA association with efficacy was investigated at predefined time points (random assignment, day 43, day 64, and day 126 [3 months after liso-cel, approximately 2 months after ASCT]) for 136 patients using ultrasensitive PhasED-Seq. ctDNA clearance (measurable residual disease [MRD]) predicted longer event-free survival (EFS) at all time points in both arms, with significantly more liso-cel-treated patients achieving MRD. Liso-cel demonstrated superior outcomes versus ASCT, including longer EFS, progression-free survival (PFS), and duration of response among patients in complete response (CR) and MRD. ctDNA re-emergence in patients with CR after ASCT confirmed its potential in predicting relapse. MRD remained significantly associated with EFS after adjusting for positron emission tomography (PET) response, while interaction testing revealed a significant interaction between PET status and treatment arm for EFS. Liso-cel achieved deeper, more durable molecular clearance by ctDNA, consistent with superior EFS and PFS versus ASCT for second-line LBCL treatment. ctDNA-MRD provided prognostic value beyond PET, supporting its role as a complementary biomarker for treatment response and relapse prediction.
PURPOSE: Cord blood transplantation (CBT) is limited by delayed hematopoietic recovery leading to frequent use of double-unit grafts. This phase II study evaluated the safety of adding dilanubicel, a cryopreserved, cord...PURPOSE: Cord blood transplantation (CBT) is limited by delayed hematopoietic recovery leading to frequent use of double-unit grafts. This phase II study evaluated the safety of adding dilanubicel, a cryopreserved, cord blood (CB)-derived, non-human leukocyte antigen-matched expanded progenitor cell product generated from pooled donors to single-unit CBT. MATERIALS AND METHODS: Between March 2022 and July 2025, we enrolled 28 patients with hematologic malignancies in this single-center phase II trial. The infusion of a matched single CB unit was followed by a target dose of 800 × 10 CD34 cells of dilanubicel. All patients received a myeloablative conditioning regimen and graft-versus-host disease (GVHD) prophylaxis consisting of cyclosporine and mycophenolate mofetil. RESULTS: The median age was 36 years (range, 10-63). Underlying diagnoses included acute leukemias (n = 25) and other hematologic malignancies (n = 3). All patients engrafted neutrophils (median, 18 days; range, 14-30) and platelets (median, 31 days; range, 26-43). Dilanubicel induced transient myelomonocytic recovery, peaking on day 7 and absent by day 14. An early lymphocyte expansion, derived exclusively from the CB graft, occurred by day 9 and peaked by day 11. No grade 3 to 4 acute or chronic GVHD was observed. At a median follow-up of 1.4 years, 27 patients remain alive and disease-free. When evaluated alongside a contemporaneous institutional cohort receiving standard single- or double-unit CBT, patients treated with dilanubicel demonstrated faster hematopoietic recovery and a markedly lower incidence of severe acute GVHD. CONCLUSION: The addition of dilanubicel to single-unit CBT demonstrated a favorable safety profile, with no severe acute or chronic GVHD, and was associated with excellent clinical outcomes. These findings support further investigation of this strategy.
Dierickx D, Heimovaara JH, Bellido M
… +13 more, Van Calsteren K, Cardonick E, Garcia AC, Baten A, Evens AM, Ferber A, Fumagalli M, Lampka E, Specht L, Vandecaveye V, Vogelius IR, Alber M, Amant F
The diagnosis and treatment of hematologic malignancies has undergone significant advancements over the past few decades, resulting in enhanced outcomes. For hematologic malignancies diagnosed during pregnancy, this pose...The diagnosis and treatment of hematologic malignancies has undergone significant advancements over the past few decades, resulting in enhanced outcomes. For hematologic malignancies diagnosed during pregnancy, this poses new questions. As possibilities continue to expand and the rising global incidence results in an increasing number of diagnoses within the pregnant population, there is a pressing need to gain a deeper understanding of the potential options for pregnant women and the impact on the newborn. As knowledge of the effects of cancer treatment increases, more women are receiving adequate cancer diagnosis and treatment during pregnancy. This paper presents an expert opinion on the use of diagnostic modalities and treatment options, including chemotherapy, radiation therapy, and immunotherapy, for acute leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, myeloproliferative neoplasms, aplastic anemia, and multiple myeloma during pregnancy.
Kulgod S, Patil BR, Kallappa S
… +13 more, Ramesh RS, Kulkarni K, Sp S, Majumdar S, Singh A, Guest C, Harris R, Aviram I, Shanbhag S, Parashar A, Ramaswamy SS, Bitan I, Kulgod A
PURPOSE: Low-cost, acceptable, high-sensitivity triage tests are needed to address low cancer prevalence in population screening, particularly in low- and middle-income countries. Breath-based canine olfaction may serve...PURPOSE: Low-cost, acceptable, high-sensitivity triage tests are needed to address low cancer prevalence in population screening, particularly in low- and middle-income countries. Breath-based canine olfaction may serve this role, but evidence, to date, has been limited to small, single-cancer studies, largely from high-income settings. We evaluated the analytical validity of a multicancer breath detection system using trained dogs integrated with Bayesian fusion modeling. METHODS: We conducted an assessor-masked, multicenter case-control study across six hospitals in Karnataka, India (CTRI/2024/10/075938). A total of 3,275 participants were enrolled (1,773 training; 1,502 testing). The test cohort included 283 treatment-naïve, biopsy-confirmed cancer cases spanning seven major cancer groups and 1,219 controls (healthy volunteers, nononcologic chronic disease, or benign biopsy). Breath was collected using cotton surgical masks, stored under -20°C cold-chain conditions, and evaluated by trained detection dogs. Individual dog indications were integrated using a Bayesian fusion framework incorporating historical dog performance and participant-level covariates. RESULTS: The fusion system achieved 90.8% sensitivity (95% CI, 87.2 to 94.5) and 91.3% specificity (95% CI, 89.7 to 92.9), with a receiver operating characteristic AUC of 0.962 (95% CI, 0.952 to 0.969). The sensitivity for early-stage disease (stage I to II) was 90.6% and remained consistent across major cancer types. CONCLUSION: In a 1,502-participant test cohort, canine olfaction combined with Bayesian fusion demonstrated high analytical accuracy for multicancer detection from breath. These findings establish analytical validity and support prospective evaluation in true screening populations.
The evaluation of novel health technologies is increasingly complicated by a landscape of pervasive social media influence and intense product marketing, factors that may distort evidence appraisal and contribute to subo...The evaluation of novel health technologies is increasingly complicated by a landscape of pervasive social media influence and intense product marketing, factors that may distort evidence appraisal and contribute to suboptimal medical decision-making and patient outcomes. Within this context, interest in histotripsy, a novel technology approved for the treatment of liver tumors, has expanded rapidly. This accelerated adoption has outpaced the available evidence, challenging established principles of safety, efficacy, and appropriate patient selection and has generated substantial debate within the oncologic community. In this editorial, we provide an overview of the technology and available data, examine the external forces contributing to its accelerated application, and propose a well established, structured, evidence-based framework to guide its rigorous evaluation, responsible adoption, and optimal clinical implementation.