Nodular Non-Hodgkin's lymphoma: the case for watchful waiting.
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Results for “watch and wait”
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Outcomes of Response-Based Watch-and-Wait and Surgical Management After Total Neoadjuvant Therapy for Rectal Cancer: A Systematic Review and Meta-analysis.
BackgroundTotal neoadjuvant therapy (TNT) increases clinical complete response rates in locally advanced rectal cancer (RC), allowing response-based management strategies such as watch-and-wait (WW) as an alternative to total mesorectal excision (TME). Outcomes associated with WW after TNT remain incompletely defined. This study aimed to compare oncologic and organ-preservation outcomes between WW and surgical management following TNT.MethodsA systematic search was conducted in PubMed, Scopus, and Cochrane Central up to April 2025. Observational studies comparing WW and TME following TNT were included. Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with I2 statistics. Secondary outcomes included tumor regrowth, salvage surgery, and permanent stoma. Risk of bias was evaluated using ROBINS-I.ResultsSix studies comprising 793 patients were analyzed. WW showed no significant difference compared with TME regarding local recurrence (OR 1.36, 95% CI 0.07-26.17; I2 = 80%), distant metastases (OR 0.62, 95% CI 0.29-1.33; I2 = 49%), 5-year disease-free survival (HR 0.97, 95% CI 0.71-1.31; I2 = 51.7%), or overall survival (HR 1.03, 95% CI 0.81-1.30; I2 = 27.9%). Permanent stoma rates were lower with WW (OR 0.12, 95% CI 0.01-1.23; I2 = 71%), becoming significant after sensitivity analysis (OR 0.04, 95% CI 0.01-0.19).ConclusionWW after TNT offers oncologic outcomes comparable to TME, with high organ preservation and reduced surgical morbidity in highly selected patients.
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Near and distance vergence facility provides complementary clinical information in concussion-related convergence insufficiency.
PURPOSE: To compare near and distance vergence facility testing in adolescents and young adults with concussion-related convergence insufficiency and evaluate changes following office-based vergence/accommodative therapy (OBVAM). METHODS: This secondary analysis of the CONCUSS randomized clinical trial evaluated vergence facility at near (40 cm) and distance (4 m) using a 12Δ base out/3Δ base in prism flipper. Participants aged 11-25 years with concussion-related convergence insufficiency were randomized to immediate or 6 weeks delayed OBVAM. Vergence facility was assessed at baseline, outcome time 1 assessment (after 12 therapy sessions for the immediate group and 6 weeks of watchful waiting for the delayed group), and outcome time 2 assessment (after both groups completed 16 therapy sessions). Agreement between near and distance vergence facility classifications was evaluated, and treatment-related changes were compared between groups. RESULTS: Of the 106 enrolled participants, 102 completed all study visits. At baseline, the near and distance vergence facility classifications demonstrated substantial discordance. Among 101 participants with both measures available, 49 demonstrated reduced distance vergence facility despite normal near vergence facility, whereas only two showed the opposite pattern (Cohen's κ = 0.12; p < 0.0001). Vergence facility improved following therapy in both treatment groups, with larger early improvements in the immediate-treatment group. CONCLUSIONS: Near and distance vergence facility testing provided complementary rather than interchangeable clinical information in adolescents and young adults with concussion-related convergence insufficiency. Both measures improved following vergence/accommodative therapy, supporting consideration of both testing distances in clinical assessment.
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Growth deceleration patterns in children with constitutional short stature: an aid to diagnosis.
A retrospective study of 263 children referred for evaluation of short stature revealed that 149 (56.7%) had constitutional short stature (CSS). A typical pattern of growth was observed in these children. As exemplified by 12 children who had complete serial growth measurements, exaggerated growth deceleration first became apparent between 3 and 6 months of age, was greatest in the first two years of life, and resulted in these children falling more than 2 SDs below the mean for height by 3 years of age. After 3 years of age, the growth rate of these children with CSS was essentially the same as that of normal children, and they ran parallel to the growth curve though below the third percentile. The importance of serial measurements and the growth chart is emphasized, and recommendations are made for the evaluation of short stature or abnormal growth deceleration in the first three years of life. Awareness of this typical pattern of growth in children without disease may aid the pediatrician in his evaluation of short stature and allow for watchful waiting when results of screening tests are normal.
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To Treat or Not to Treat: Navigating Early-Stage CLL in the Era of Targeted Therapy.
Chronic lymphocytic leukemia (CLL) is most frequently diagnosed at early, asymptomatic stages (Rai 0/Binet A), in which a watch-and-wait strategy remains the standard of care, based on historical trials demonstrating no overall survival benefit from early treatment. Over the past two decades, however, substantial advances in genomic profiling-including immunoglobulin heavy-chain variable region (IGHV) mutational status, TP53 disruption, recurrent gene mutations, and complex karyotype-have uncovered marked biological heterogeneity among early-stage patients and substantially improved prediction of disease progression. In parallel, targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors and venetoclax-based combinations have transformed the management of symptomatic CLL, raising renewed interest in whether early intervention might favorably alter the natural history of biologically high-risk disease. In this review, we critically examine the evolution of prognostication in early-stage CLL, integrate contemporary molecular and clinical risk models, and summarize evidence from both historical chemotherapy-era studies and modern early-intervention trials. We discuss key unresolved controversies, including reliance on surrogate endpoints, the risks of overtreatment, and the persistent absence of an overall survival benefit across all early-treatment strategies. Finally, we outline future research priorities, including refined genomic stratification, minimal residual disease-driven (MRD)-driven approaches, and combination targeted therapies currently under investigation. Despite renewed interest in preemptive treatment, available evidence supports continued observation for asymptomatic patients outside clinical trials.
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Integrative Genomic Profiling of Newly Diagnosed Prostate Cancers Progressing on Surveillance.
OBJECTIVE: To identify molecular features associated with earlier progression to definitive therapy amongst patients with localized prostate cancer (PCa) managed on active surveillance (AS). METHODS: We performed a retrospective pilot study of 7 patients with low- to intermediate-risk PCa undergoing serial multiparametric MRI (mpMRI)-targeted biopsies of the same lesion while on AS, who all proceeded to definitive therapy. Time-to-treatment (TTT) was defined as years from first biopsy on AS to definitive therapy. Laser-capture microdissection was used to separate tumor epithelium, benign glands, high-grade prostatic intraepithelial neoplasia, and stroma in each biopsy specimen. DNA from the tumor and matched benign tissue underwent whole-exome sequencing, and RNA from all compartments underwent whole-transcriptome sequencing. Somatic mutations and copy-number alterations were compared across serial biopsies and used to reconstruct phylogenies and quantify clonal complexity. RESULTS: Tumors exhibited substantial intratumoral heterogeneity, and in 3 of 6 paired cases, serial mpMRI-targeted biopsies showed discordant somatic profiles consistent with sampling distinct major clones over time. By contrast, no single gene-level alteration, and few large-scale chromosomal events, were associated with TTT. High clonal complexity, defined as ≥3 subclones, was associated with significantly shorter TTT than low complexity (median 1.9 vs 7.2 years; P = .0082). Exploratory pathway analyses of individual tissue components suggested TTT-associated differences in inflammatory signaling and stromal-epithelial cross-talk. CONCLUSION: In this small, hypothesis-generating cohort, clonal complexity was more closely associated with earlier definitive therapy than individual genomic alterations. Larger prospective studies are needed to validate whether multiomic measures of clonal architecture can improve AS risk stratification.
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Integrating clinical and genomic features to predict response to neoadjuvant therapy in microsatellite-stable rectal cancer.
BACKGROUND: Neoadjuvant therapy (NAT) has shifted rectal cancer management toward organ preservation. However, achieving a complete response (CR) for "watch-and-wait" strategies is hindered by high response heterogeneity. Although immunotherapy-combined NAT has expanded the candidate pools, the predictive significance of molecular alterations remains unclear. OBJECTIVES: This study aimed to evaluate clinical and genomic profiles of rectal cancer patients undergoing NAT to identify response predictors and to develop a nomogram for estimating CR probability. DESIGN: Retrospective, single-center cohort study. METHODS: This study included 437 patients with rectal adenocarcinoma at Fudan University Shanghai Cancer Center between December 2019 and March 2023. Patients underwent paired tumor and germline genomic sequencing (887-gene panel) before NAT. Logistic and Cox regression analyses were performed to identify clinical and genetic risk factors associated with tumor response and long-term survival. RESULTS: Of the 437 patients, 96.6% had microsatellite-stable (MSS) tumors. In the MSS locally advanced rectal cancer cohort (N = 307), the CR rate was 35.5%. Multivariate analysis identified immunotherapy-combined NAT (iTNT) (OR 4.41, 95% CI: 2.42-8.27), SYNE1 mutation (OR 2.12, 95% CI: 1.06-4.26), negative mesorectal fascia (MRF) status (OR 0.34, 95% CI: 0.17-0.66), and lower tumor location (OR 0.48, 95% CI: 0.27-0.84) as independent predictors of CR. KRAS mutation was the sole independent predictor of reduced disease-free survival (DFS; HR 1.93, 95% CI: (1.11-3.36), p = 0.020). KRAS G12D subtype was associated with the worst 2-year distant metastasis-free survival (71.3%) and exhibited a distinct predilection for lung metastasis. The clinical-genomic nomogram yielded strong discrimination (AUC = 0.705) and calibration, with favorable DCA net benefit. CONCLUSION: Clinical and genomic features jointly determine outcomes in MSS rectal cancer. SYNE1 mutation serves as a novel biomarker for CR, while KRAS mutations, especially the G12D subtype, identify patients at high risk for systemic relapse. The clinical-genomic nomogram facilitates individualized selection for organ-preservation strategies.
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