Compare the radiological characteristics of screening images preceding interval cancers that occurred in women screened with digital breast tomosynthesis (DBT) plus digital mammography (DM) vs. those in women screened with DM alone. From two randomized trials comparing DBT + DM vs. DM, 91 (43 from DBT + DM arm and 48 from DM arm) images preceding interval cancers and 190 (94 and 96, respectively) negative controls were reviewed by three radiologists using only DM screening mammograms and by three different radiologists using all available images, i.e. DBT and DM for the experimental arm and DM for the standard arm. The cancers were classified according to the number of reviewers that found abnormalities, as true negative (negative for all three reviewers), minimal sign (positive for one and negative for two), and false negative (positive for two or three reviewers). In the DM arm, interval cancers were classified as true negative in 29–42
Background. Daratumumab-bortezomib-melphalan-prednisone (DVMP) and daratumumab-lenalidomide-dexamethasone (DRd) are standard treatments for transplant-ineligible (NTE) newly diagnosed multiple myeloma (NDMM) patients (pts). No prospective randomized trial has directly compared DVMP vs DRd. Moreover, real-life older NTE pts are underrepresented in clinical trials. Aims. We conducted a randomized multicenter phase IV trial (NCT03829371; funded by the Italian Medicines Agency AIFA - Independent Research) to compare safety and efficacy of VMP +/- daratumumab (DVMP) vs Rd +/- daratumumab (DRd) in an unselected real-life population of NTE NDMM pts. Methods. In the first part of the trial, NDMM pts who were NTE due to age ≥65 years or comorbidities were randomized 1:1 to 9 VMP cycles vs continuous Rd (standard approved schedule). As of July 2022, the protocol was amended to randomize 1:1 pts to DVMP vs DRd. Pts were enrolled regardless of performance status, comorbidities, renal function or baseline laboratory values. Stratification was based on IMWG frailty score and cytogenetic risk [high risk: del(17p), t(14;16) or t(4;14)]. The primary endpoint was progression-free survival (PFS) in the intention-to-treat (ITT) population. Key secondary endpoints included overall survival (OS). Centralized measurable residual disease by next-generation flow (NGF-MRD) was performed in daratumumab-treated pts. In this analysis we focus on data of the daratumumab-treated cohort. Results. At data cut-off (July 9, 2025), 170 pts received DVMP (n=87) or DRd (83). Baseline characteristics were balanced between DVMP and DRd arms: median age was 76 (range 64–90) vs 76 years (range 63–87); 18% vs 13% of pts were aged >80 years; 37% vs 34% were frail; 27% vs 32% had high-risk cytogenetics. At a median follow-up of 19.3 months, no significant PFS differences were observed between DVMP vs DRd in the ITT population (HR 1.56, 95% CI 0.72–3.33, p=0.30; Figure). No significant differences were observed across age (> or ≤80 years), IMWG frailty score or cytogenetic-defined risk subgroups. The 6-month and 1-year PFS rates were 90% vs 97% and 83% vs 90% with DVMP vs DRd. In the first 6 months, 9 PFS events (2 progressive disease and 7 deaths) were observed [7/9 (78%) pts were frail; 7/9 (78%) events were observed in the DVMP arm]. In the ITT population, the 12-month NGF-MRD negativity rate was 25% with DVMP vs 30% with DRd (OR 1.79, 95% CI 0.81–3.94, p=0.15). Reaching MRD negativity within 12 months led to an improved PFS (vs MRD positivity: HR 0.12, 95% CI 0.03–0.50, p=0.004). No new safety concerns were reported. Conclusion. We confirmed the efficacy of DVMP and DRd in an older real-life NTE NDMM population including ~35% of frail pts. At current follow-up, no significant PFS differences were observed between DVMP and DRd, but early mortality was more frequent in frail and DVMP-treated pts. Centralized MRD assessment in this real-life setting was feasible, and MRD negativity rates were comparable to those in registrational trials.
PURPOSE:In 2009, a regional audit on ovarian cancer in the Regional Cancer Care Network (RCCN) of Piemonte (Italy) documented that patients were widely distributed across different treatment centers, with evidence of suboptimal care. We present the re-audit and feedback (A&F) intervention performed in 2016-2020 and the variation on quality of care and outcomes. METHODS:An A&F intervention was implemented across gynecologic units treating ovarian cancer in Piemonte. Key recommendations and indicators were identified from international guidelines. Global adherence to guideline recommendations was measured as the mean percentage of adherence across all the indicators. Data were collected retrospectively (May-December 2016, baseline period) and prospectively (May 2017-September 2020). Change in adherence to recommendations over time was monitored and feedback provided during quarterly meetings. Overall survival was identified as clinical outcome. RESULTS:Among 1,030 women (77% advanced stage), the global adherence to guidelines increased by 2.1% (95% CI, 1.6 to 2.6) every 6 months, from 51.3% to 70.4%. The likelihood of treatment in high-volume surgical centers and multidisciplinary team discussions before treatment increased over time (odds ratio [OR], 1.15 [95% CI, 1.08 to 1.21] and OR, 1.21 [95% CI, 1.15 to 1.28]). Five-year survival was 47% overall (87% among early and 35% among advanced stages). Although no consistent trend in survival was observed during the A&F period, a 10% increase in global adherence was associated with improved 5-year survival (hazard ratio, 0.91 [95% CI, 0.87 to 0.95]). CONCLUSION:The implementation of this A&F initiative was associated with improvements in quality-of-care indicators for ovarian cancer, highlighting the potential value of A&F methodologies to support quality improvement activities.
OBJECTIVES:A key element in ensuring appropriate balance of harms and benefits in cancer screening is to develop a priority set of performance and outcome indicators to be used in screening data evaluation systems. These indicators need to be equity-focused, aligned to new screening approaches and broad-based to cover possible opportunistic screening, but at the same time as limited as possible. STUDY DESIGN:Indicators for breast, colorectal and cervical cancer screening programs were chosen through a consensus building Delphi methodology involving a panel of cancer screening experts. METHODS:The list of indicators was developed using a multistage process. First, a systematic search was performed along with an extensive grey literature search to identify all potential existing indicators. Next, these indicators were refined by two expert groups, definitions and calculations were agreed upon, redundant indicators removed. A final list of 38 indicators was put forward into a Delphi study. 33 cancer screening experts were invited to take part. The Delphi study consisted of two rounds of an online survey and an online facilitated discussion between the cancer screening experts. RESULTS:23 indicators were chosen covering 10 predefined indicator categories with detection rate, examination coverage and interval cancer rate deemed most important. Outcome indicators such as crude incidence rate and time from screen to result notification, while ultimately reaching consensus were deemed of less importance. CONCLUSION:23 priority indicators cover the entire screening pathway including harms, barriers and inequalities. These indicators have been piloted by the CanScreen-ECIS project.
