Citations

Abstract Introduction: With over 80, 000 new cases of non-Hodgkin's lymphoma (NHL) diagnosed annually, modifiable risk factors remain unclear. Circadian disruption, linked to cancers like breast and prostate, affects immune cells (e.g., natural killer cells and T-helper cells) by altering their trafficking and proliferation. Some studies (PMID: 30566672, 27611440) suggest long sleep may increase overall NHL risk, including a Mendelian randomization (MR) study (PMID: 32895918). However, no research has examined the causal relationship between sleep traits, including long sleep, and NHL risk, by subtypes. We hypothesize that sleep traits are causally associated with NHL subtypes in European populations, testing this using MR with data from the International Lymphoma Epidemiology Consortium (InterLymph). Methods: We conducted two-sample MR using genome-wide association studies (GWAS) summary data for sleep traits and NHL subtypes. Only independent, genome-wide significant (p < 5×10-8) Single Nucleotide Polymorphisms (SNPs) were selected as valid instruments, sourced from the UK Biobank. Sleep traits included chronotype (153 SNPs), insomnia (48 SNPs), sleep duration (78 SNPs), excessive daytime sleepiness (37 SNPs), short sleep (27 SNPs), and long sleep (8 SNPs). NHL subtype data were from InterLymph: follicular lymphoma (6, 508 cases / 64, 183 controls), mantle cell lymphoma (1, 169 cases / 61, 603 controls), Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL: 1, 697 cases / 59, 333 controls), and chronic lymphocytic leukemia (8, 522 cases / 67, 653 controls). The primary analysis used inverse-variance weighted (IVW) random-effects, with MR-Egger for pleiotropy adjustment. Results: Using the IVW method, we did not identify any statistically significant causal association between sleep traits and the risk of NHL subtypes, but did yield several intriguing trends. Long sleep (sleep duration >= 9 h per night) showed a marginally increased NHL risk [Odds ratio (OR) range: 1.51 - 247.9] across each subtype. Short sleep (sleep duration < 7 h per night) showed a similar trend [OR range: 1.25 - 1.81], except for WM/LPL, where we noticed a negative trend. The confidence limit for long sleep was imprecise due to the small number of variants. We did not notice any significant directional horizontal pleiotropy or weak instrument bias. Conclusions: We found no conclusive evidence of a relationship between sleep traits and four NHL subtypes. However, we see suggestive trends of long and short sleep associated with higher risk of some NHL subtypes. These findings align with the previous studies, which showed long sleep was associated with higher risk of NHL overall. Future directions include expanding our analysis to additional NHL subtypes, generating polygenic risk scores, and conducting stratified analyses. Citation Format: Pankhil Shah, Brittany Crawford, Anwar Merchant, Brenda Birmann, Angelica Macauda, Michelle A. Hildebrandt, Aaron Norman, Neil E. Caporaso, Meredith Yeager, Michael Dean, Immaculata De Vivo, Lynn Goldin, Nicola J. Camp, Rosalie Griffin, Delphine Casabonne, Federico Canzian, Pelin Unal, Elad Ziv, Catherine R. Marinac, Alexandra Nieters, Stephen J. Chanock, Mitchell J. Machiela, Michael Conry, Charlie Zhong, Hanla A. Park, Simon Cheah, Jonathan N. Hofmann, Elizabeth E. Brown, Celine Vachon, Susan Slager, Sonja Berndt, Sophia S. Wang, Vijai Joseph, James McKay, Henrik Hjalgrim, Lara Sucheston-Campbell, Karl Smith-Byrne, Alyssa Clay-Gilmour. Association between sleep traits and risk of non-Hodgkin's lymphoma subtypes: a mendelian randomization study in the International Lymphoma Epidemiology (InterLymph) Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7415.

Study Design: Analysis of prospectively collected data. Objective: To assess if systemic illness severity affects cervical spondylotic myelopathy (CSM) surgery outcomes. Summary of Background Data: It remains unclear if CSM patients with poor physical status/severe systemic illness benefit as much from surgery as those in good condition. Methods: Using the Quality Outcomes Database CSM cohort and the American Association of Anesthesiology (ASA) grade as a surrogate for illness burden, we compared patients with (ASA 3–4) and without (ASA 1–2) severe systemic illness, including rates of readmission and 24-month minimal clinically important differences (MCID) achievement for patient-reported outcomes (PROs)—numerical rating score (NRS) arm and neck pain, neck pain-related disability (NDI), and quality of life (EQ-5D). Results: Of 1141 CSM patients, 1062 had ASA grades recorded. Of these 1062 patients, 70.2% had a 2-year follow-up for mJOA, and 81%–84% had a follow-up for NRS arm and neck, NDI, and EQ-5D. Five hundred twenty-one patients (49.1%) had mild (ASA 1–2) and 541 (50.9%) had severe systemic illness (ASA 3–4). The severe disease cohort was older (63.3±11.0 vs. 57.4±11.7), had higher BMI (31.4±7.0 vs. 28.9±5.6), had more comorbidities (diabetes, coronary artery disease, depression), and had less independent ambulation (71.3% vs. 90.6%) ( P <0.05). At baseline, severe disease patients had worse NRS arm (5.2±3.5 vs. 4.7±3.4) and neck (5.5±3.2 vs. 5.1±3.3) pain, NDI (40.5±20.1 vs. 36.8±21.0), and EQ-5D (0.53±0.22 vs. 0.59±0.22) scores ( P <0.05). Perioperatively, the severe disease cohort had longer hospitalizations (2.4±2.6 vs. 1.7±2.0 days) and increased nonhome discharges (17% vs. 5%) ( P <0.05). The severe disease cohort had higher 90-day readmissions (7.6% vs. 2.5%), including surgery-related (3.7% vs. 1.5%) and non–surgery-related reasons (3.9% vs. 1.0%) ( P <0.05). On multivariate analysis, increased ASA grade was significantly associated with 90-day readmissions (OR: 2.55 per 1-grade increase, 95% CI: 1.38–4.83). However, both severe and mild disease cohorts had similarly high rates of achieving 2-year MCID for mJOA (67.5% vs. 66.0%), NRS arm (72.0% vs. 74.1%), neck (69.5% vs. 69.4%) pain, NDI (63.1% vs. 68.1%), and EQ-5D (67.9% vs. 66.9%) ( P >0.05). Conclusion: Patients with severe systemic illness (higher ASA) have worse baseline PROs and higher 90-day readmissions. However, they achieve similar MCID rates for mJOA and all measured PROs 2 years postoperatively.

Abstract Introduction: Breast cancer genome-wide association studies (GWAS) have identified over 200 susceptibility loci, many replicated in diverse populations. However, cross-ancestry evaluation of breast cancer genetic architecture remains limited. We examined breast cancer genetic architecture using GWAS summary results from European (EUR; cases (ca) = 188,474, controls (co) = 96,201), East Asian (EAS; ca = 20,393, co = 86,329), African American (AA; ca = 9,235, co = 10,184), and US Hispanic/Latina and Latin American (H/L; ca = 2,396, co =7,468) studies. Methods: GWAS results were derived from the Breast Cancer Association Consortium, the African Ancestry Breast Cancer Genetics Consortium (AABCG), Biobank Japan, and a meta-analysis of five studies of H/L women with breast cancer. Linkage disequilibrium (LD) scores were generated for EUR, EAS, and AMR using the 1000 Genomes Project, while AA LD scores were derived from a subset of AABCG controls. Heritability was estimated for each ancestry group using LD score regression. Genetic correlations between populations were assessed via Popcorn. Polygenicity was analyzed using GENESIS; however, due to the limited sample size in the H/L studies, these estimates were restricted to AA, EAS, and EUR. Enrichment of heritability across regulatory elements was evaluated using stratified LD score regression across all populations. Results: The logit-scale heritability and corresponding standard error (SE) were 0.466 (0.066) for EAS, 0.501 (0.050) for EUR, 0.588 (0.360) for H/L, and 0.614 (0.095) for AA. The estimated number of independent susceptibility loci was 4,446 for EAS, 5,235 for EUR, and 8,308 for AA. Using a clumping and thresholding approach, an optimal set of common variants were projected to explain 38.6% (EUR), 39.4% (EAS), and 26.2% (AA) of genetic variance for samples of 100,000 cases and 100,000 controls with AUCs from corresponding estimated polygenic risk scores (PRSs) of 0.621 (EUR), 0.634 (EAS), and 0.611 (AA). Genetic correlations were strongest between EUR and EAS (ρ = 0.79, SE = 0.08) and EUR and H/L (ρ = 0.68, SE = 0.21), and weakest between AA and EAS (ρ = 0.42, SE = 0.14) and AA and H/L (ρ = 0.26, SE = 0.24). Among 73 genomic features, we found significant (P &lt; 0.05/73) enrichment in heritability in EUR for ‘ancient promoter’ regions, transcription factor binding sites, H3K4me3, ‘super-enhancers’, H3K4me1, H3K27ac; in EAS for ‘super-enhancers’; and in AA for H3K27ac. No genomic features were significantly enriched in H/L, likely due to limited power. Conclusion: These findings suggest a shared breast cancer genetic architecture across diverse populations, as well as the potential for a similar level of breast cancer risk stratification by PRS in these populations. Expanding GWAS in underrepresented populations is essential to improve genetic risk predictions and foster equitable cancer prevention. Citation Format: James L. Li, Maria Zanti, Jacob Williams, Om Jahagirdar, Guochong Jia, Qiang Hu, Jean-Tristan Brandenburg, Li Yan, Weang-Kee Ho, Jingmei Li, José P. Miranda, Devika Godbole, Julie-Alexia Dias, Leila Dorling, Wenlong C. Chen, Nicholas Boddicker, Ying Wang, Alicia Martin, Martin J. Zhang, Yan Zhang, Joe Dennis, Esther M. John, Gabriela Torres-Mejia, Larry Kushi, Jeffrey Weitzel, Susan L. Neuhausen, Luis Carvajal-Carmona, Christopher Haiman, Elad Ziv, Laura Fejerman, Wei Zheng, Dezheng Huo, Douglas Easton, Nilanjan Chatterjee, Peter Kraft, Montserrat Garcia-Closas, Wendy Wong, Kyriaki Michailidou, Qianqian Zhu, Diptavo Dutta, Thomas U. Ahearn, Haoyu Zhang. Genetic architecture of breast cancer across diverse populations: Assessing heritability, genetic correlation, and polygenicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2282.

ImportanceThe safety and effectiveness of combining surgical peripheral iridectomy (SPI) with goniosynechialysis (GSL) and goniotomy (GT) vs trabeculectomy for intraocular pressure (IOP) reduction remains unknown.ObjectiveTo investigate the safety and effectiveness at 1 year of SPI + GSL + GT vs trabeculectomy in advanced primary angle-closure glaucoma (PACG) without cataract.Design, Setting, and ParticipantsThis noninferiority randomized clinical trial was conducted at 8 tertiary eye centers in China. A total of 88 Chinese patients (88 eyes) with advanced PACG without cataract were enrolled from January 2022 to July 2023. Data were analyzed from August 2024 to September 2024. Mean (SD) patient age was 60.3 (7.3) years, and 52 patients (59.1%) were female. Forty-three patients were randomized to SPI + GSL + GT and 45 were randomized to trabeculectomy; 86 patients (97.7%) completed the 12-month follow-up.InterventionsParticipants were randomized 1:1 to receive SPI + GSL + GT or trabeculectomy.Main Outcomes and MeasuresThe primary outcome was IOP at 12 months (noninferior margin: 4 mm Hg). Secondary outcomes included surgical success (IOP: 5-18 mm Hg, ≥20% reduction from baseline, with or without antiglaucoma medications); postoperative complications and interventions, including bleb massage, suture lysis, or releasable sutures; and number of antiglaucomatous medications prescribed.ResultsAt 12 months, the SPI + GSL + GT group had a mean (SD) IOP of 15.6 (4.0) mm Hg vs 14.9 (4.2) mm Hg in the trabeculectomy group (difference, 0.5 mm Hg; 95% CI, −1.2 to 2.2; P = .55), which was within the 4-mm Hg noninferiority margin. Qualified success rates were 38 of 43 participants (88.4%) for SPI + GSL + GT and 42 of 45 participants (93.3%) for trabeculectomy (difference, −5.0%; 95% CI, −19.6% to 8.5%; P = .48). However, complete success rates were lower in the SPI + GSL + GT group (26 participants [60.5%]) vs the trabeculectomy group (37 participants [82.2%]; difference, −21.8%; 95% CI, −40.2% to −2.4%; P = .03). Postoperative complications were present for 8 participants (18.6%) in the SPI + GSL + GT group vs 9 participants (20.0%) in the trabeculectomy group (difference, −1.4%; 95% CI, −17.9% to 15.1%; P = .71). Postoperative interventions were lower in the SPI + GSL + GT group (3 participants [7.0%] vs 25 participants [55.6%]; difference, 48.6%; 95% CI, 32.2%-65.0%; P &amp;lt; .001). Median (IQR) numbers of medications used decreased from 2 (0-3) to 0 (0-1) in the SPI + GSL + GT group and from 2 (2-3) to 0 (0-0) in the trabeculectomy group (difference, −0.81; 95% CI, −1.36 to −0.26; P = .004).Conclusions and RelevanceIn this randomized clinical trial among patients with advanced PACG without cataract, SPI + GSL + GT demonstrated noninferiority (4-mm Hg margin) to trabeculectomy for IOP at 12 months, with fewer interventions (including bleb massage, suture lysis, or releasable sutures) but no difference in postoperative medication use. This suggests SPI + GSL + GT as a potential alternative to trabeculectomy for similar cases, pending validation in larger sample sizes with smaller noninferiority margins.Trial RegistrationClinicalTrials.gov Identifier: NCT05163951

ImportanceIntraocular pressure (IOP) reduction with phacogoniotomy (phacoemulsification plus goniosynechialysis plus goniotomy) was not less than that of phacotrabeculectomy for advanced primary angle-closure glaucoma (PACG) with cataract at 1-year follow-up, but longer-term outcomes are needed.ObjectiveTo investigate if phacogoniotomy is noninferior to phacotrabeculectomy for advanced PACG with cataract at 2 years.Design, Setting, and ParticipantsThis multicenter, noninferiority, randomized clinical trial took place in 7 ophthalmology centers in China. The trial started May 31, 2021, and 2-year follow-up ended May 31, 2024. Included in this analysis were patients with advanced PACG and cataract. Study data were analyzed from September 2024 to January 2025.InterventionsRandom assignment (1:1) to phacogoniotomy or phacotrabeculectomy.Main Outcomes and MeasuresThe primary outcome measure was reduction in IOP from baseline to the 2-year visit with a noninferiority margin of 4 mm Hg.ResultsA total of 124 participants (124 eyes) were randomized (mean [SD] age, 66.4 [8.6] years; 67 female [54.0%]), 65 (52.4%) to the phacogoniotomy group and 59 (47.6%) to the phacotrabeculectomy group. A total of 59 patients (90.7%) in the phacogoniotomy group and 52 patients (88.1%) in the phacotrabeculectomy group completed 2-year visits. All participants were Chinese. Mean (SD) IOP reduction was −25.6 (10.2) mm Hg and −24.7 (9.4) mm Hg in the phacogoniotomy and phacotrabeculectomy groups, respectively, and the upper boundary of the CI for difference in change between groups was lower than the 4-mm Hg noninferiority margin (mean difference, −0.5 mm Hg; 97.5% CI, −1.7 mm Hg to 0.8 mm Hg; P = .42). The mean difference for complete success for phacogoniotomy vs phacotrabeculectomy was −6.7% (95% CI, −21.4% to 8.8%; P = .47) and for qualified success was 1.4% (95% CI, −11.0% to 14.3%, P = .30). Median (IQR) number of antiglaucomatous medication was 0 (0) vs 0 (0; Hodges-Lehmann estimate of location shift, 0; 95% CI, 0; P =.12) with phacogoniotomy vs phacotrabeculectomy, respectively (mean difference, 0.13; 95% CI, −0.36 to 0.63; P = .60).Conclusions and RelevanceMean IOP reduction with phacogoniotomy was noninferior to phacotrabeculectomy for advanced PACG and cataract at 2-year follow-up with no differences detected in complete or qualified success or mean number of antiglaucomatous medications. These findings support phacogoniotomy as an alternative to phacotrabeculectomy for patients with advanced PACG and cataract.Trial registrationClinicalTrials.gov Identifier: NCT04878458

ABSTRACTThe optimal conditioning schedule and CD34+ cell dose for autologous stem cell transplantation (ASCT) for AL amyloidosis is unknown. Patients (n = 1704) who underwent ASCT for AL amyloidosis between 2003 and 2020 in 9 centers were included. Data on melphalan conditioning dose, number of conditioning days, whether a rest day between conditioning and stem cell infusion was given or not, and infused CD34+ cell dose were collected. Full‐dose melphalan (≥ 180 mg/m2) was administered in 63.7% of the patients, and 80.4% had melphalan split into 2‐day conditioning. A rest day (day −1) between the conditioning regimen and stem cell infusion was provided in 52.5% of patients. The median infused CD34+ cell count was 4.7 × 106/kg. An infused CD34+ cell count ≥ 4.5 × 106/kg was associated with a shorter time to neutrophil and platelet engraftment. In a nominal regression analysis, full‐dose melphalan, 1‐day melphalan conditioning, and omitting a rest day between conditioning and stem cell infusion were independent predictors of post‐ASCT higher deep hematological response. The median follow‐up was 8.6 years, and 38% of patients died. Independent predictors of superior overall survival in multivariate Cox regression analysis included full‐dose melphalan, having no rest day, and infused CD34+ cells ≥ 4.5 × 106/kg. Independent predictors of higher day‐100 transplant‐related mortality (TRM) in nominal logistic regression analysis included poorer performance status, NT‐proBNP/BNP ≥ 1800/400 pg/mL, serum albumin < 2.5 g/dL, CD34+ cells < 4.5 × 106/kg, and not having a rest day. In conclusion, 1 day of melphalan conditioning and administration of CD34+ cells ≥ 4.5 × 106/kg are recommended for ASCT in AL amyloidosis.

BACKGROUND: Data registries lack a definitive classification system that distinguishes different locations of colon cancer from one another. OBJECTIVE: To establish an international consensus on the definition of primary colon cancer segment locations. DESIGN: Between December 2022 and June 2023, Delphi survey study was conducted to seek opinions from relevant international experts and eventually develop a consensus definition of each colon cancer segment. SETTING: Three-round online-based Delphi survey study. INTERVENTIONS: Online survey included 17 questions. In the first two rounds, participating experts were asked to rank each statement on a scale of 1–9 (9 is the most relevant). Consensus statements and definitions were revised according to results, obtaining a consensus score of 7–9. During the third round and online meeting, definitions and statements reached a moderate or high consensus(above 4 in more than 70% of participants) were included. MAIN OUTCOME AND MEASURE: Primary goal of our project was focused on precisely localizing the specific segment affected by primary colon cancer, rather than to identify surgical treatment or type of resection needed for particular segment. RESULTS: The first round included 331 experts, 301 (91%) completed the second round, and 295 (98%) completed the final round. Experts strongly supported the use of a “10 cm rule” to describe colon cancer sites at the flexures and anatomical landmarks for other segments. Regarding the definition of rectosigmoid cancer, experts from America and Europe reached a high consensus that the term rectosigmoid as a colon cancer location must be abolished in contrast to experts from Asia. Description of cancers overlapping segments achieved a consensus of 64%. LIMITATIONS: Subjective decisions are based on individual expert clinical experience. CONCLUSIONS: This Delphi survey, the first internationally conducted consensus study, achieved a remarkable level of consensus among a panel of global experts. Ambiguity still exists regarding overlapping lesions. See Video Abstract .

The NCCN Guidelines for Testicular Cancer provide recommendations for the multidisciplinary approach to the diagnostic workup, treatment, and follow-up for testicular germ cell tumors, including both seminoma and nonseminoma. These NCCN Guidelines Insights discuss the current treatment recommendations and supporting clinical data for seminomas as presented in Version 2.2025 of the NCCN Guidelines for Testicular Cancer.

Ewing sarcoma and osteosarcoma constitute 36% of all primary bone cancers. However, these 2 subtypes represent the most commonly diagnosed bone cancer types in the pediatric and adolescent population. Although still largely unknown, certain genetic mutations, rearrangements, and/or predisposition syndromes likely play a role in the pathogenesis of bone cancer. Osteosarcoma may also develop as a direct result of the long-term side effects of radiation therapy. With the implementation of a multimodality approach to treatment, including multiagent neoadjuvant and adjuvant chemotherapy regimens, targeted therapy options, surgery, and radiation, individuals with Ewing sarcoma and osteosarcoma are showing higher cure rates and improved overall survival. The NCCN Guidelines for Bone Cancer provide a consensus and evidence-based framework for the workup, management, and surveillance of local and recurrent/metastatic disease.

Abstract Outcomes of bispecific antibodies in patients with renal impairment (RI) are not well characterized, given the exclusion of these patients from clinical trials. Herein, we evaluated patients with relapsed/refractory multiple myeloma and RI treated with standard-of-care teclistamab. RI was defined as creatinine clearance (CrCl) &lt;40 mL/min. CrCl &lt;30 mL/min or dialysis dependence was defined as severe RI. Of the 384 included patients, 81 (21%) had RI, including 45 (18%) with severe RI, and 18 (5%) on dialysis. Patients with RI were more likely to be older (median age, 71 vs 67 years; P = .002) and have a higher median number of previous lines of therapy (7 vs 6; P = .04). Rates and severity of cytokine release syndrome (51% vs 59%; grade ≥3: 1.2% vs 1%) and immune effector cell–associated neurotoxicity syndrome (16% vs 13%; grade ≥3: 2.5% vs 2.6%) were similar in patients with and without RI, respectively. Patients with RI had higher baseline and day 30 post-teclistamab grade ≥3 anemia and grade ≥3 thrombocytopenia. Renal function did not worsen after teclistamab initiation in most patients with RI outside of the context of disease progression. Overall response rate (52% vs 56%; P = .61) and survival outcomes (median progression-free survival, 4.6 vs 6.5 months; P = .62) were comparable in patients with and without RI, respectively, after a median follow-up of 9.9 months. No differences in overall survival or non-relapse mortality were noted. Our findings suggest that treatment with teclistamab is feasible in patients with RI, including those on dialysis, with a similar safety and efficacy profile to patients without RI.