Citations

Abstract Introduction Minimally invasive surgical techniques including Robotic-Assisted thoracoscopic surgery (RATS) have advanced the treatment of lung cancer and enhanced patient outcomes from early recovery to improved quality of life. The “July effect” hypothesizes that morbidity and mortality outcomes worsen during the beginning of academic year when new residents and fellows begin training. We investigated the impact of the same on outcomes of RATS among lung cancer patients. Methods Using the National Inpatient Sample (2016-2019), we identified adults(ages≥18 years) with lung cancer who underwent RATS(lobectomy/sublobar resection) at urban teaching centers(UTC). Patients were stratified by surgical timing: July-September versus other months. Multivariable logistic regression compared perioperative outcomes between groups, adjusting for confounders. Results We analyzed 25,480 RATS procedures, with 25.59% performed during July-September. Baseline characteristics were comparable between groups regarding sex, race (White, Hispanic), insurance type, comorbidity burden, and age; however, fewer Black patients underwent surgery during July-September (Table 1a). Multivariable logistic regression revealed no significant differences in perioperative outcomes between the July-September and other months of the year. Evaluated outcomes included thoracic complications like pneumonia (aOR 0.89, 95% CI 0.62-1.28, p = 0.526), pneumothorax (aOR 1.07, 95% CI 0.85-1.34, p = 0.583), air leak (aOR 0.98, 95% CI 0.79- 1.22, p = 0.873), respiratory failure (aOR 0.9, 95% CI 0.50-1.63, p = 0.729) , atelectasis (aOR 1.12, 95% CI 0.88-1.42, p = 0.372), thromboembolic events like pulmonary embolism (aOR 0.63, 95% CI 0.13-2.97, p = 0.557), deep venous thrombosis (aOR 1.01, 95% CI 0.65-1.57, p = 0.952), bleeding complications like transfusion (aOR 0.95, 95% CI 0.55-1.64, p = 0.866), hemothorax/hemoperitoneum/hematoma (aOR 0.58, 95% CI 0.22-1.52, p = 0.264), renal complications (aOR 1.00, 95% CI 0.32-3.17, p = 0.994), conversion to open surgery (aOR 0.53, 95% CI 0.11-2.47, p = 0.417), extended length of stay (>7 days) (aOR 0.96, 95% CI 0.78-1.17, p = 0.667), and in-hospital mortality (aOR 0.57, 95% CI 0.21-1.50, p = 0.250)(Table 1b). Conclusions Our study suggested no “July effect” in the perioperative outcomes of RATS. This demonstrates the robust hospital support systems ensuring the safe transition of resident classes without affecting the patient care negatively. This abstract is funded by: None

Abstract Introduction The lung is the most commonly affected organ in sarcoidosis, present in over 90% of cases. However, cardiac involvement may also occur and can significantly complicate patient outcomes. We propose to explore further. Methods Adults with isolated pulmonary sarcoidosis and combined pulmonary-cardiac sarcoidosis were identified using ICD-10 codes from the National Inpatient Sample (2016-2022). Patients with any additional organ involvement beyond lung or heart were excluded to ensure distinct comparison groups. We compared age, sex, race, insurance type, hospital characteristics, comorbidities, and healthcare burden between groups. Results Over the seven-year study period, we identified 154,125 hospitalizations of patients with either isolated pulmonary or combined pulmonary-cardiac sarcoidosis. Of these, 2.41% (n = 3,715) were combined pulmonary-cardiac cases, while the remainder were isolated pulmonary sarcoidosis. Patients with combined pulmonary-cardiac sarcoidosis were significantly younger(mean age: 58.2 vs. 62.0 years, p < 0.001), but had a higher mean Charlson Comorbidity Index (CCI) score (3.49 vs. 2.77, p < 0.001) compared to those with isolated pulmonary disease. Multiple demographic differences were found: isolated pulmonary cases were predominantly female(59.5%), with a higher proportion of White patients(46.7%), whereas combined cases were predominantly male(60.4%), with a higher proportion of Black patients(53.0%). Both groups were primarily covered by Medicare(58.1% of isolated vs. 48.1% of combined), with a higher proportion of combined pulmonary-cardiac sarcoidosis cases treated at urban teaching centers(92.3% vs. 78.9%, p < 0.001). Patients with combined pulmonary-cardiac sarcoidosis demonstrated a higher prevalence of multiple comorbidities, including chronic kidney disease, prior myocardial infarction, complete atrioventricular block, obstructive sleep apnea, congestive heart failure, peripheral vascular disease, and valvular disease. Conversely, the prevalence of chronic obstructive pulmonary disease was lower in this group. Hospitalization burden was substantially greater among patients with combined pulmonary-cardiac sarcoidosis (Charlson Comorbidity Index 2.77±0.01 vs. 3.49±0.07), evidenced by longer mean length of stay (6.1±0.05 vs. 7.6±0.32 days) and significantly higher total hospital charges ($82,987±1,121 vs. $122,460±6,991) (Table 1). Conclusions Combined pulmonary-cardiac sarcoidosis affected younger patients with greater comorbidity and hospitalization burden, with notable racial disparities. As cardiac sarcoidosis is frequently underdiagnosed, systematic cardiac screening protocols in high-risk sarcoidosis patients are essential for earlier detection and improved management. This abstract is funded by: None

PURPOSE External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT. METHODS We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-naïve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS. RESULTS Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-naïve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death. CONCLUSION To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel’s discussions on select 2026 updates to the guidelines regarding nonmetastatic disease: the elimination of the very-low-risk group, updates to the Principles of Active Surveillance, and caution in the use of focal therapy in newly diagnosed patients.

Abstract Hyperpolarized [1-¹³C]pyruvate MRI provides real-time, radiation-free insight into myocardial pyruvate metabolism and mitochondrial oxidative capacity, yet its utility in patients with severe multivessel coronary artery disease before and after surgical revascularization remains unknown. Here we show, in the first prospective study applying this technique to three-vessel disease, that serial imaging is feasible and safe with no serious adverse events in 22 injections. Healthy myocardium displayed a bicarbonate-to-total hyperpolarized carbon product ratio of 0.66 ± 0.13, indicating that the majority of pyruvate undergoes oxidation. Patients exhibited significantly lower ratios in the inferolateral segment (P = 0.03) with reciprocal increases in lactate, and global ratios correlated with left ventricular ejection fraction (r = 0.695, P = 0.006). Post-revascularization changes were heterogeneous across individuals. These findings establish hyperpolarized 13C MRI as a powerful tool for noninvasive assessment of myocardial metabolism in multivessel coronary artery disease and support its potential for longitudinal therapeutic monitoring.

PURPOSE Remote symptom monitoring using patient-reported outcomes (PROs) has been shown to improve symptom control and physical function among patients with advanced cancer. However, it is unclear whether these benefits are similar across demographic groups. This exploratory analysis of the PRO-TECT trial examined whether the effects of electronic symptom monitoring varied by race, age, sex, and educational attainment. METHODS PRO-TECT was a cluster randomized trial conducted across 52 US community oncology practices comparing weekly electronic symptom monitoring with usual care (UC). Adult patients with metastatic solid tumors receiving systemic therapy were enrolled (N = 1,191). Participants in the PRO arm completed weekly symptom surveys including the PRO-CTCAE, triggering alerts to the care team for severe or worsening symptoms. Patients chose whether to complete weekly PROs online or via telephone-based interactive voice response not requiring Internet access. Outcomes were measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 symptom control and physical function scales. Subgroup analyses were performed by race (Black v White), age (<65 v ≥65 years), sex (male v female), and educational attainment (≤high school v >high school). RESULTS From baseline to 3 months, PRO participants showed greater improvements in symptom control (+2.37 v −0.20, P = .002) and physical function (+1.54 v −0.93, P = .02) versus UC. Benefits were most pronounced among younger, female, Black, and less educated participants. Black participants in the PRO arm were more likely to report that symptom reporting made them feel more in control of their care compared with White participants. CONCLUSION Electronic symptom monitoring improved quality-of-life outcomes overall, including among groups who have historically experienced higher symptom burden or barriers to communication. Remote PRO systems may represent an equitable strategy to enhance cancer care delivery.

Background The optimal management of biochemical recurrence (BCR) after radical prostatectomy (RP) remains controversial, particularly in the absence of clinical or radiographic evidence of disease. Salvage radiotherapy (SRT) remains standard of care, but it is unclear whether SRT benefits patients when modern imaging with a multiparametric magnetic resonance imaging (mpMRI) and prostate‐specific membrane antigen‐positron emission tomography/computed tomography (PSMA‐PET/CT) are negative for local recurrence. Retrospective data comparing SRT to observation for such patients is fraught with selection bias, underscoring the need for a prospective randomised controlled trial. Study Design and Methods The Biochemical Recurrence Irradiation or Observation (BRIO) is a randomised study under the DIVINE trial framework (NCT06378866) enrolling men with BCR (prostate‐specific antigen [PSA] level ≥0.2, up to 1.5 ng/mL) after RP with no radiographic evidence of recurrence on mpMRI and PSMA‐PET/CT. Major inclusion criteria include age ≥18 years, biochemically recurrent prostate cancer after RP with a PSA level between 0.2 and 1.5 ng/mL, and no local or metastatic recurrence on imaging. A total of 312 patients will be enrolled. Participants are randomised 1:1 to standard‐of‐care SRT followed by surveillance (Group A), or initial observation with subsequent image‐guided therapy at radiographic progression (Group B). Based on historical analysis, a total of 30 metastasis events provides 80% power to detect a significant improvement (hazard ratio 0.5 corresponding to a 5‐year metastasis‐free proportion of 80.7% in the control group and 89.8% in the experimental group with one‐sided type I error rate of 0.15). All participants undergo baseline blood collection to measure prostate cancer‐extracellular vesicles and cell‐free DNA for biomarker development. Participants are followed in a 16‐week cycle with serial PSA measurements, repeat imaging if PSA doubles, safety assessment, and patient‐reported outcomes. Endpoints The primary endpoint is distant recurrence‐free survival at 5‐years using a 12‐month landmark to mitigate bias arising from differing assessment schedules for patients receiving optional 6 months of androgen deprivation therapy. Key secondary outcomes include time to hormone therapy, quality of life measures, adverse effects, and novel blood and urine biomarkers. Conclusion The BRIO study will clarify the clinical benefit of immediate SRT vs observation with image‐guided intervention in mpMRI and PET‐negative BCR after RP.

Summary Cancer genome sequencing is essential for understanding tumor evolution and advancing precision medicine. 1 However, reference gaps and germline variants obscure detection of small and large somatic variants and methylation in repetitive regions. 1–3 It is common for tumor cells to gain or lose chromosome arms due to somatic structural changes that occur inside highly repetitive satellite DNA sequences in the centromeres. 4 To identify the full spectrum of somatic variants, including complex rearrangements, we construct and curate near-complete, haplotype-resolved assemblies of the most recent common ancestor of an early-passage broadly-consented hypodiploid pancreatic cancer cell line and matched normal tissues. The tumor assembly completely recapitulates all 35 tumor chromosomes observed with karyotyping, with multiple translocation-induced hybrid chromosomes. The hybrid chromosomes contain putative functional dicentric and fused centromeres, nested foldback inversions causing 14 breakpoints with a haplotype switch in a single event, and centromeric satellite tandem duplications up to 136 kbp. Direct comparison of tumor and normal assembly haplotypes uncovers >7,000 variants altering >1 Mbp of sequence in repetitive regions that have been hidden by reference gaps and germline variants. 44 % of somatic small variants change representation because they alter germline variants on GRCh38, impacting mutational signatures and kataegis/omikli clusters. Most somatic LINE insertions originate from two hypomethylated non-reference germline LINE insertions, highlighting their impact on insertion mutation burden. These assemblies demonstrate that centromeric, acrocentric, and telomeric regions conventionally excluded from analysis harbor extensive somatic and epigenetic changes. Resolving complete tumor genomes enables a deeper understanding of cancer structural plasticity and the endpoints of breakage-fusion-bridge cycles. These assembled, curated paired normal-tumor benchmarks will serve as a critical foundation for developing future algorithms to characterize the most intractable regions of cancer genomes.

Abstract Solitary plasmacytoma of bone (SPB) is a localized plasma cell neoplasm associated with a substantial risk of progression to multiple myeloma (MM), yet the role of adjuvant systemic therapy following definitive radiation therapy (RT) remains undefined. We conducted a randomized phase III trial (Alliance A061402) to evaluate whether the addition of systemic therapy with ixazomib, lenalidomide, and dexamethasone (IXA-LEN-DEX) to zoledronic acid (ZA) improves outcomes compared with ZA alone in patients with SPB and minimal (< 10%) bone marrow plasma cell involvement following RT. Patients were randomized to receive six 28-day cycles of IXA-LEN-DEX-ZA or ZA alone. The primary endpoint was time to progression (TTP) to MM. The study was closed early due to poor accrual after enrolling 11 patients (IXA-LEN-DEX-ZA, n = 5; ZA, n = 6). All patients completed RT and planned treatment without dose reductions. The combination regimen was well tolerated, with limited grade ≥ 3 toxicities, including hypophosphatemia and lymphopenia. At follow-up extending beyond 4 years, the 1- and 4-year progression rates to MM in the IXA-LEN-DEX-ZA arm were 0% and 33%, respectively, compared with 37.5% and 58.3% at 1 and 2 years in the ZA-alone arm. Although underpowered, these findings demonstrate the feasibility and tolerability of an all-oral adjuvant systemic regimen in SPB and provide prospective data supporting further investigation of systemic strategies to delay progression to MM.