Measurable Residual Disease and Clinical Outcomes in Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis.

Importance: Measurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development. Objective: To assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment. Data Sources: Clinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023. Study Selection: Prospective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded. Data Extraction and Synthesis: Study sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted. Main Outcomes and Measures: Analyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model. Results: A total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40). Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.

First Bite Syndrome in Transoral Surgery for Oropharyngeal Cancer.

OBJECTIVE: First bite syndrome (FBS) is a rare complication of transoral surgery (TOS) for oropharyngeal cancer (oropharyngeal squamous cell carcinoma [OPSCC]). Risk factors for developing this complication are not well described. In this study, we attempt to identify risks for developing FBS in TOS. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care medical center. METHODS: This study was exempted by the Mayo Clinic institutional review board. We performed a review from January 2017 to November 2022 of all patients who underwent TOS for OPSCC by a single provider. Exclusion criteria included less than 6 months follow up, prior treatment of head and neck cancer, or incomplete records. Demographic data, comorbidities, tumor characteristics, surgical details, adjuvant treatment details, functional outcomes, and oncologic outcomes were assessed. Fisher's Exact test and Kruskal-Wallis rank sum test were used to identify significant variables, and multivariable logistic regression was used to address confounding. RESULTS: One hundred and one patients were identified. Eighty-nine met the inclusion criteria. The mean follow-up was 34 months (median 33). Seven patients (7.9%) developed FBS. Palatine tumor primary (P = .041), resection of styloglossus/stylopharyngeus (P = .039), and parapharyngeal fat manipulation (P = .015) were associated with the presence of FBS. After adjusting for tumor location, manipulation of parapharyngeal fat maintained significance (P = .025). T and N staging, tumor volume, adjuvant radiation, and ligation of lingual/facial arteries were not associated with the development of FBS. Eighty-six percent (6/7) of patients had a resolution of FBS at an average of 11.3 months. CONCLUSION: Manipulation of the parapharyngeal space is independently associated with developing FBS in TOS in our cohort. Further confirmatory studies are warranted.

Effect of palatine tonsil tumor resection on postoperative velopharyngeal insufficiency in transoral surgery.

BACKGROUND: Velopharyngeal insufficiency (VPI) is a known complication of transoral surgery (TOS) for oropharyngeal HPV-mediated squamous cell carcinoma. Controversy exists regarding adequate resection margins for balancing functional and oncologic outcomes. METHODS: This retrospective study was exempted by the IRB. Patients who underwent TOS from January 2017 to October 2022 were included. Patient characteristics, treatment details, and oncologic and functional outcomes were evaluated. RESULTS: Fifty-five patients were included. Mean and median follow-up was 34 months. 98% of patients were AJCC stage I/II. Recurrence-free survival was 96% with no local recurrences. Univariate analysis demonstrated an association between VPI and pT stage (p = 0.035), medial pterygoid resection (p = 0.049), and palatal attachment sacrifice (p < 0.001). Multivariate analysis showed sacrifice of the palatal attachments remained a significant risk for VPI (p = 0.009). CONCLUSION: Loss of soft palate pharyngeal attachments is an independent risk factor for VPI. When oncologically appropriate, the palatal attachments to the pharynx may be preserved.

Resting-State Functional Magnetic Resonance Imaging Network Association With Mortality, Epilepsy, Cognition, and Motor Two-Year Outcomes in Suspected Severe Neonatal Acute Brain Injury.

BACKGROUND AND OBJECTIVES: In acute brain injury of neonates, resting-state functional magnetic resonance imaging (MRI) (RS) showed incremental association with consciousness, mortality, cognitive and motor development, and epilepsy, with correction for multiple comparisons, at six months postgestation in neonates with suspected acute brain injury (ABI). However, there are relatively few developmental milestones at six months to benchmark against, thus, we extended this cohort study to evaluate two-year outcomes. METHODS: In 40 consecutive neonates with ABI and RS, ordinal scores of resting-state networks; MRI, magnetic resonance spectroscopy, and electroencephalography; and up to 42-month outcomes of mortality, general and motor development, Pediatric Cerebral Performance Category Scale (PCPC), and epilepsy informed associations between tests and outcomes. RESULTS: Mean gestational age was 37.8 weeks, 68% were male, and 60% had hypoxic-ischemic encephalopathy. Three died in-hospital, four at six to 42 months, and five were lost to follow-up. Associations included basal ganglia network with PCPC (P = 0.0003), all-mortality (P = 0.005), and motor (P = 0.0004); language/frontoparietal network with developmental delay (P = 0.009), PCPC (P = 0.006), and all-mortality (P = 0.01); default mode network with developmental delay (P = 0.003), PCPC (P = 0.004), neonatal intensive care unit mortality (P = 0.01), and motor (P = 0.009); RS seizure onset zone with epilepsy (P = 0.01); and anatomic MRI with epilepsy (P = 0.01). CONCLUSION: For the first time, at any age, resting state functional MRI in ABI is associated with long-term epilepsy and RSNs predicted mortality in neonates. Severity of RSN abnormality was associated with incrementally worsened neurodevelopment including cognition, language, and motor function over two years.

Risk Factors in Patients Who Had Prior Renal or Liver Transplant Undergoing Primary Total Knee Arthroplasty.

BACKGROUND: More solid organ transplant (SOT) patients are undergoing total knee arthroplasty (TKA). This study identifies risk factors for complications, implant survivorship, and mortality in TKA patients who had prior SOT. METHODS: We identified 176 TKAs in patients who had prior SOT. Of these, 77 had a prior renal (RT), 77 had a prior liver (LT) transplant, and 22 had multiple prior transplants (MT). Median survival was estimated using Kaplan-Meier. Univariate analyses were assessed with mixed-effects logistic regressions for complications and Cox-regressions for mortality. Median follow-up was 63 months (range, 24 to 109). RESULTS: At least one acute medical complication occurred in 25, 13, and 27% of cases with prior RT, LT, and MT, respectively (P = .12). None of the variables were significantly associated with acute medical complications. At least one surgical complication occurred in 14, 13 and 14% of cases with prior RT, LT, and MT, respectively (P = 1). Vitamin D supplementation (Odds Ratio [OR] = 0.38, P < .03) was associated with lower risk of surgical complications. Reoperation and revision rates were 5 and 3%, respectively. Older age at time of transplantation and greater level of serum creatinine at time of TKA were associated with lower risk (OR = 0.96, P = .01), and higher risk of reoperation (OR = 4.9, P = .01), respectively. Coronary artery disease was associated with higher mortality (Hazard Ratio = 2.35, P = .01). CONCLUSIONS: Vitamin D was associated with lower surgical complications, whereas a younger age at time of transplantation increased the risk of reoperation. Additionally, SOT patients with coronary artery disease demonstrated higher mortality after TKA.