Citations

Abstract Objective The validity of progression-free survival (PFS) as a surrogate for overall survival (OS) in the antibody-drug conjugate (ADCs) era remains uncertain. We evaluated the association between treatment effects on PFS and OS in randomized trials of ADCs for metastatic breast cancer (mBC) and explored the surrogate threshold effect (STE). Methods PubMed, Embase, Cochrane, and ClinicalTrials.gov were searched for published randomized controlled phase II–IV trials evaluating ADCs in mBC and reporting hazard ratios (HRs) for both PFS and OS. A meta-epidemiological approach was used. The primary metric was the ratio of hazard ratios (rHR = HR_PFS/ HR_OS), with rHR < 1 indicating a larger effect on PFS. Trial-level associations were assessed using weighted linear regression (R²) and Spearman’s correlation. Results Twenty-one trials (n = 21; 18 phase III) evaluating nine ADCs were included. The pooled rHR was 0.79 (95% CI, 0.73–0.86), indicating a larger relative effect on PFS than OS. Numerically, the largest discrepancies were observed in triple-negative disease (rHR 0.72) and trials allowing crossover (rHR 0.71). Concordant statistical significance between endpoints occurred in 76% of the trials, whereas 24% showed a significant PFS benefit without OS improvement. The trial-level association between PFS and OS was moderate (R² = 0.62; ρ = 0.67). Conclusion Treatment effects on PFS consistently exceeded those on OS, although effect directions were highly concordant between endpoints. These findings provide an exploratory framework to contextualize the relationship between PFS and OS in ADC trials, requiring further validation in diverse clinical settings.

Abstract Introduction Patients with metastatic spine disease (MSD) present with varying degrees of systemic illness and frailty. Given the palliative intent of surgery and radiation treatment for MSD, treatment risks must be judiciously weighed against potential benefits. We sought to examine the impact of peroperative nutritional status as measured by the PG-SGA on survival in patients undergoing surgery and radiation for MSD. Methods This study involved an international, multicenter prospective, observational registry of patients with MSD: AO Knowledge Forum Tumor’s Metastatic Tumor Research and Outcomes Network (MTRON). Variables including baseline demographics, oncologic data, adverse events (medical adverse events and surgical complications), length of stay, and nutritional status were prospectively collected. The Patient-Generated Subjective Global Assessment (PG-SGA) was used to evaluate nutritional status. Results A total of 589 patients were included in this study; 469 (80%) of whom underwent surgery and radiation and 120 (20%) of whom underwent radiation alone. The majority of patients (362, 61%) were classified as well nourished, however, 68 patients (12%) were classified as severely malnourished. Among patients that underwent surgery and radiation, the median overall survival of well nourished patients was 491 days compared to 117 days in the severely malnourished patients (p < 0.001). A multivariate analysis demonstrated severe malnourishment and ECOG performance status of 3 or 4 were associated with worse overall survival. Conclusion Malnutrition as measured by the PG-SGA demonstrated to be significantly and independently associated with perioperative survival in patients with MSD. Further studies that investigate optimal pre-treatment optimization for patients with MSD in order to mitigate morbidity and mortality risk are essential.

Abstract Background Distal (ileal) metabolic bariatric surgeries (DMBS) have gained increasing adoption due to their enhanced metabolic effects. However, the absence of standardized definitions, classification, and clinical indications limits their consistent application. This consensus aimed to establish an international consensus on the definition, classification, indications, and postoperative management of DMBS. Methods A three-round modified Delphi study was conducted including international expert surgeons from 16 countries. A total of 98 statements were developed across three domains: procedural characteristics, patient selection, and postoperative follow-up. Consensus was defined as ≥75% agreement. Statements not reaching consensus were revised and resubmitted. Results Consensus was achieved on 81 statements. DMBS were defined as procedures involving gastro-ileal or duodeno-ileal bypass, emphasizing ileal stimulation as a key metabolic mechanism. Procedures with a common channel ≤350 cm, including single-anastomosis duodenal-ileal with SG (SADI-S), single anastomosis sleeve-ileal transit bipartition (SASI), sleeve gastrectomy with Roux-en-Y transit bipartition (SG+TB), and biliopancreatic diversion with duodenal switch (BPD-DS), as well as one-anastomosis gastric bypass (OAGB) with biliopancreatic limb > 50% of total small bowel length were classified as DMBS. Routine measurement of total small bowel length was strongly recommended. DMBS were considered appropriate as primary procedures in patients with BMI ≥40 kg/m² with comorbidities, a BMI ≥50–60 kg/m², irrespective of the presence of comorbidities, and as revisional options for suboptimal clinical response (SoCR), recurrent weight gain (RWG), or persistent metabolic disease. Comprehensive preoperative and multidisciplinary evaluation was deemed mandatory, and liver cirrhosis, heart failure, end-stage kidney disease, and inflammatory bowel disease were considered contraindications. Postoperative care requires lifelong multidisciplinary follow-up, with increased attention to nutritional deficiencies and supplementation. Conclusions This consensus provides a standardized framework for DMBS, supporting harmonization of practice and improved patient safety.

Among patients with treatment-naive hepatocellular carcinoma, glass microsphere radiation segmentectomy before liver transplant achieved high rates of complete pathologic necrosis, which was positively associated with the number of optimized treatment parameter thresholds.

Pulsed Electric Field (PEF) ablation is a non-thermal cancer treatment that disrupts tumor cell membranes while preserving the immune microenvironment and promoting immunogenic cell death. We present a case of a patient with metastatic hormone receptor-positive, HER2-low breast cancer who achieved a durable clinical response after PEF in combination with an immune checkpoint inhibitor (pembrolizumab). The patient remained off systemic therapy for 14 months without disease progression. Single-cell spatial molecular imaging (SMI) and gene set enrichment analysis (GSEA) were performed to evaluate immune microenvironment changes pre- and post-PEF treatment. Spatial transcriptomics of the tumor cell compartment revealed a post-PEF enrichment of immune-related pathways, including interferon alpha/beta and gamma signaling and MHC class I antigen processing and presentation, alongside increased infiltration of immune cells: CD8+ T cells, plasmablasts, and monocytes within the tumor neighborhood. This hypothesis-generating case suggests PEF’s potential to reshape the tumor-immune microenvironment when combined with immune checkpoint blockade, warranting further studies on its role in combination immunotherapy strategies.

Management of unstable upper lumbar fractures with corpectomy and posterior fixation is technically demanding, and conventional workflows may require intraoperative repositioning, increasing operative complexity. Lateral mini-open upper lumbar corpectomy (LMULC) paired with robotic-assisted (RA) posterior percutaneous pedicle screw fixation (PPPSF) can be performed in a single position to facilitate ventral spinal decompression and stabilization in the anatomically constrained upper lumbar spine. In this study, we describe the operative technique and report four illustrative cases of unstable L1 or L2 fractures treated with single-position LMULC, RA-PPPSF, and short-segment fusion. Clinical, radiological, intraoperative variables and postoperative outcomes were evaluated. The mean age was 52.3 ± 17.7 years. The median operation time was 314 min (range 268–361 min); the median estimated blood loss (EBL) was 225 mL (range 100–400 mL). The median preoperative kyphosis was 10.15° (range 8.4–14.6°), the median postoperative kyphosis measured 6.65° (range 1.7–10.8°) and the median correction achieved was 3.5° (range −2.4–12.9°). The median visual analog scale (VAS) pain score reduced from 7 (range 7–9) preoperatively to 4.5 (range 2–6) postoperatively at discharge. At a median follow-up of 12 months (range 6–15 months), all patients had uncomplicated recoveries, demonstrated solid fusion on imaging, and reported favorable MacNab outcomes. Single-position LMULC with RA-PPPSF was technically feasible in this preliminary illustrative series and resulted in favorable clinical and radiographic outcomes. However, further studies in larger cohorts are warranted to help confirm these findings and better define the potential advantages and limitations of this technique.

Introduction/Objectives: House call programs provide care for homebound patients. We conducted a case-control study to compare hospitalization and/or emergency department (ED) use by patients enrolled in a primary care house call program versus ambulatory (community-dwelling) patients. Methods: Program enrollees (cases) were matched by age and self-reported gender to community-dwelling patients (controls). The primary exposure was the combination of hospitalization and/or ED visits for 1 year before the index date (October 1, 2024). We used unadjusted and adjusted conditional logistic regression to determine differences in health care use. Results: We identified 26 cases (median [range] age, 84 [66-98] years; 16 [62%] female) and 130 controls. All cases had 4 or more chronic diseases, as compared with 87 (67%) of controls ( P = .003). A higher proportion of cases than controls had previous hospitalization and/or ED visits (84.6% vs 27.7%; P < .001). After adjusting for the number of chronic illnesses, no differences in previous hospitalization and/or ED use were identified between groups. Conclusions: Cases had more chronic illnesses and more hospitalizations and/or ED visits than community-dwelling controls. The comorbid health burden of participants in the house call program drove greater health care use and justifies a higher level of care for this medically complex patient population.

Abstract Vertebral metastatic disease results from many types of cancer and can have a devastating impact on patient mobility, psychological health, quality of life, and ultimately overall patient survival. However, the development of radiotherapy and surgical techniques has rapidly surged in conjunction with ongoing advances in basic science and translational studies. In this review, we discuss the paradigm shift in our understanding of the epidemiology and treatment algorithms for spinal oncology, ranging from preoperative optimization strategies, radiation and surgical techniques, the utilization of molecular markers and targeted therapeutics in medical oncology, and prognostication tools that underscore a new multidisciplinary approach to spinal oncology care.

Abstract Introduction Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen (ER), progesterone (PR), and HER2 expression. It accounts for ∼15% of breast cancers and is more common in Black women, younger patients, and those with BRCA1 mutations. TNBC carries a poor prognosis with 5-year survival rates of 92% (localized), 66.8% (regional), and 14.3% (metastatic). Patients with high-risk of recurrence can be treated with different adjuvant therapies based on results of 3 trials (capecitabine, pembrolizumab, olaparib), but data on adverse events (AE) on their combination is limited.High-risk, stage II-III TNBC is treated with curative intent using neoadjuvant chemotherapy with pembrolizumab, followed by surgery and radiation. Pembrolizumab, an anti-PD-1 checkpoint inhibitor, was FDA-approved in 2021 based on KEYNOTE-522. This phase III trial showed that pembrolizumab plus chemotherapy significantly improved pathologic complete response (pCR) and event-free survival (EFS). 3-year EFS was 84.5% vs. 76.8% with placebo (HR 0.63); 5-year follow-up confirmed sustained benefit, with OS of 86.6%. Patients achieving pCR had better outcomes, while those with residual disease remained at high risk for recurrence, justifying further adjuvant therapy.In KEYNOTE-522, grade ≥3 treatment-related (AEs occurred in 77.1% receiving pembrolizumab-chemotherapy vs. 73.3% with placebo-chemotherapy. Pembrolizumab was linked to more serious AEs (34.1% vs. 20.1%) and higher discontinuation rates (23.3% vs. 12.3%). Before pembrolizumab, capecitabine was standard of care for TNBC with residual disease, based on the CREATE-X trial (HR 0.52 for OS benefit). Common AEs included hand-foot syndrome, fatigue, and liver enzyme elevation. Notably, KEYNOTE-522 excluded adjuvant capecitabine, and CREATE-X predated the use of pembrolizumab. Olaparib, a PARP inhibitor, was FDA-approved in 2022 for high-risk early TNBC with germline BRCA mutations, based on OlympiA. It improved invasive disease-free and OS. Grade ≥3 AEs included anemia, neutropenia, and fatigue. OlympiA did not include pembrolizumab or capecitabine, limiting insight into optimal sequencing or combination. Currently, no trials compare pembrolizumab, capecitabine, or olaparib directly, nor do they guide how to sequence or combine these therapies. Despite NCCN guidelines allowing combined/sequential use in high-risk patients, real-world safety and outcome data are lacking. This study aims to evaluate and compare the safety and effectiveness of capecitabine, olaparib, pembrolizumab, and their combinations. We will describe AE rates, onset, discontinuation, and dose modifications to inform clinical management and help reduce early termination of effective therapies. Methods We conducted a retrospective observational study across all Mayo Clinic sites. Eligible patients were ≥18 years with early-stage TNBC who initiated adjuvant therapy with capecitabine, pembrolizumab, olaparib, or combinations (capecitabine + pembrolizumab or olaparib + pembrolizumab) from October 2018 to September 2024. Patients with metastatic disease, other active malignancies, or receiving concurrent investigational therapy were excluded. The primary outcomes were incidence and timing of treatment-related AEs. Secondary outcomes included time to AE resolution, immune-related AEs, treatment interruptions/modifications, early discontinuation, and EFS. Time-to-event data will be analyzed using Kaplan-Meier and Cox proportional hazards models. Subgroup analyses by age, DPYD status, regimen, and dosing will be conducted. Data was abstracted from electronic health records and managed using REDCap. Results Data collection is completed. Final analyses are being conducted, and results will be presented at SABCS 2025. Citation Format: R. Garza-Morales, F. Raheem, D. Alton, S. Sharma, B. Murad, W. Harris, E. Terwilliger, F. Batalini. Analysis of Adverse Events and Outcomes of Adjuvant Therapies in TNBC as Monotherapy and Combination: Pembrolizumab, Capecitabine, and Olaparib [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-10-06.