Uterine-sparing laparoscopic lateral suspension in the treatment of pelvic organ prolapse.

AIM: Apical prolapse is an important component of pelvic organ prolapse. The aim of our study was to investigate the effectiveness of laparoscopic lateral suspension (LLS) surgery, which we performed while sparing the uterus. METHODS: LLS surgery was performed on 62 patients due to apical prolapse, preserving their uterus. The patients' pelvic organ prolapse quantification system (POP-Q) points and sexual function using pelvic organ prolapse/urinary incontinence sexual function questionnaire (PISQ-12) prior to and 12 months following the surgery were compared, and the results were evaluated. RESULTS: The POP-Q points and PISQ-12 scores evaluating sexual function of the patients who underwent LLS were significantly improved compared to pre-operation values (p Ë‚ 0.001). No intraoperative complications were observed in the patients. Recurrence was observed in 6 (9.6%) of 62 total cases in post-operative follow-up. Apical prolapse was seen in two patients (3.2%), and anterior vaginal wall recurrence was observed in one patient (1.6%). Posterior vaginal wall recurrence was seen in three patients (4.8%). Pelvic pain complications were observed in four patients (6.4%) in the postoperative follow-up. Mesh erosion was not observed in any of the cases. It was observed that 5 (38%) of 13 patients with stress urinary incontinence (SUI) had improved SUI complaints after surgery. The mean operation time was 66.3 ± 12.3 min. CONCLUSION: LLS is an effective and safe method for patients with apical prolapse who want to preserve their uterus. LLS can be applied as an alternative to the sacrocolpopexy procedure, which has risks such as potentially serious neurological and life-threatening vascular injury in the sacral region.

Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

PURPOSE: As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies. PATIENTS AND METHODS: Patient-level clinical and ctDNA data were pooled and harmonized from 200 patients across five independent clinical trials investigating the treatment of patients with non-small-cell lung cancer with programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1)-directed monotherapy or in combination with chemotherapy. CtDNA levels were measured using different ctDNA assays across the studies. Maximum variant allele frequencies were calculated using all somatic tumor-derived variants in each unique patient sample to correlate ctDNA changes with overall survival (OS) and progression-free survival (PFS). RESULTS: We observed strong associations between reductions in ctDNA levels from on-treatment liquid biopsies with improved OS (OS; hazard ratio, 2.28; 95% CI, 1.62 to 3.20; P < .001) and PFS (PFS; hazard ratio 1.76; 95% CI, 1.31 to 2.36; P < .001). Changes in the maximum variant allele frequencies ctDNA values showed strong association across different outcomes. CONCLUSION: In this pooled analysis of five independent clinical trials, consistent and robust associations between reductions in ctDNA and outcomes were found across multiple end points assessed in patients with non-small-cell lung cancer treated with an ICI. Additional tumor types, stages, and drug classes should be included in future analyses to further validate this. CtDNA may serve as an important tool in clinical development and an early indicator of treatment benefit.

Early Assessment of Molecular Progression and Response by Whole-genome Circulating Tumor DNA in Advanced Solid Tumors.

Treatment response assessment for patients with advanced solid tumors is complex and existing methods require greater precision. Current guidelines rely on imaging, which has known limitations, including the time required to show a deterministic change in target lesions. Serial changes in whole-genome (WG) circulating tumor DNA (ctDNA) were used to assess response or resistance to treatment early in the treatment course. Ninety-six patients with advanced cancer were prospectively enrolled (91 analyzed and 5 excluded), and blood was collected before and after initiation of a new, systemic treatment. Plasma cell-free DNA libraries were prepared for either WG or WG bisulfite sequencing. Longitudinal changes in the fraction of ctDNA were quantified to retrospectively identify molecular progression (MP) or major molecular response (MMR). Study endpoints were concordance with first follow-up imaging (FFUI) and stratification of progression-free survival (PFS) and overall survival (OS). Patients with MP (n = 13) had significantly shorter PFS (median 62 days vs. 310 days) and OS (255 days vs. not reached). Sensitivity for MP to identify clinical progression was 54% and specificity was 100%. MP calls were from samples taken a median of 28 days into treatment and 39 days before FFUI. Patients with MMR (n = 27) had significantly longer PFS and OS compared with those with neither call (n = 51). These results demonstrated that ctDNA changes early after treatment initiation inform response to treatment and correlate with long-term clinical outcomes. Once validated, molecular response assessment can enable early treatment change minimizing side effects and costs associated with additional cycles of ineffective treatment.