The outcome of patients with metastatic tumors who discontinued immune checkpoint inhibitors (ICIs) not for progressive disease (PD) has been poorly explored. We performed a meta-analysis of all studies reporting the clinical outcome of patients who discontinued ICIs for reasons other than PD. We searched PubMed, Embase and Scopus databases, from the inception of each database to December 2023, for clinical trials (randomized or not) and observational studies assessing PD-(L)1 and CTLA-4 inhibitors in patients with metastatic solid tumors who discontinued treatment for reasons other than PD. Each study had to provide swimmer plots or Kaplan-Meier survival curves enabling the reconstruction of individual patient-level data on progression-free survival (PFS) following the discontinuation of immunotherapy. The primary endpoint was PFS from the date of treatment discontinuation overall and according to tumor histotype, type of treatment and reason of discontinuation. The Combersure's method was used to estimate meta-analytical non-parametric summary survival curves assuming random effects at study level. Thirty-six studies (2180 patients) were included. The pooled median PFS (mPFS) was 24.7 months (95% CI, 18.8-30.6) and the PFS-rate at 12, 24, and 36 months was respectively 69.8% (95% CI, 63.1-77.3), 51.0% (95% CI, 43.4-59.8) and 34.0% (95% CI, 27.0-42.9). Univariable analysis showed that the mPFS was significantly longer for patients with melanoma (43.0 months), as compared with non-small cell lung cancer (NSCLC, 13.5 months) and renal cell carcinoma (RCC, 10.0 months; between-strata comparison test p-value < 0.001); for patients treated with anti-PD-(L)1 + anti-CTLA-4 as compared with anti-PD-(L)1 monotherapy (44.6 versus 19.9 months; p-value < 0.001), and in NSCLC when the reason of treatment discontinuation was elective as compared with toxicity onset (19.6 versus 4.8 months; p-value = 0.003). The multivariable analysis confirmed these differences. The long-term outcome of patients who stopped ICIs for reasons other than PD was substantially affected by clinicopathological features: PFS after treatment discontinuation was longer in patients with melanoma, and/or treated with anti-PD-(L)1 + anti-CTLA-4, and shorter in patients with RCC or in those patients with NSCLC who stopped treatment for toxicity onset. The Italian Ministry of University and Research (PRIN 2022Y7HHNW).

The primary aim of our study was to assess the main mammographic and ultrasonographic features of invasive male breast malignancies. The secondary aim was to evaluate whether a specific radiological presentation would be associated with a worse receptor profile. Radiological images (mammography and/or ultrasound) of all patients who underwent surgery for male invasive breast cancer in our institution between 2008 and 2023 were retrospectively analyzed by two breast radiologists in consensus. All significant features of radiological presentation known in the literature were re-evaluated. Fifty-six patients were selected. The mean age at surgery of patients was 69 years (range: 35–81); in 82% of cases (46 patients), the histologic outcome was invasive ductal carcinoma. A total of 28 out of 56 (50%) patients had preoperative mammography; in 9/28 cases (32%), we found a mass with microcalcifications on mammography. The mass presented high density in 25 out of 28 patients (89%); the mass showed irregular margins in 15/28 (54%) cases. A total of 46 out of 56 patients had preoperative ultrasounds. The lesion showed a solid mass in 41/46 (89%) cases. In 5/46 patients (11%), the lesion was a mass with a mixed (partly liquid–partly solid) structure. We did not find any statistically significant correlation between major types of radiological presentation and tumor receptor arrangement. Knowledge of the main radiologic presentation patterns of malignant male breast neoplasm can help better manage this type of disease, which is rare but whose incidence is increasing.

Background: The surrogacy of overall response rate (ORR) or progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing antibody-drugs conjugates (ADC) has never been investigated. Methods: RCTs testing ADCs in patients with advanced solid tumors and reporting data on OS and PFS and/or ORR were analyzed. The main objective was to assess the trial-level association between the surrogate endpoints (ORR or PFS) and the reference endpoint (OS), overall and in subgroups of trials defined by tumor type, number of previous lines of systemic treatments, and specific ADC features. Results: Twenty-five RCTs, for a total of 26 treatment comparisons and 11 729 patients, were included in the analysis. In 21 comparisons the ADC was administered as monotherapy, and in 16 was tested in patients with breast cancer. The association between the hazard ratio for OS and relative risk of ORR was moderate: the R2 from a model adjusted by tumor type was 0.47 (95% CI = 0.11 to 0.83). The association between the hazard ratios for OS and PFS was strong: the R2 from the adjusted model was 0.79 (95% CI = 0.66 to 0.92). Cross-validation analyses showed similar results. Consistent results were obtained across all the subgroups analyzed, with the notable exception of the subgroup of trials testing ADCs for breast cancer, where the association between OS and ORR appeared strong (R2 = 0.77; 95% CI = 0.51 to 0.90). Conclusions: In RCTs evaluating ADCs in advanced solid tumors, PFS serves as a robust surrogate endpoint for OS, offering greater reliability than ORR and adequately supporting accelerated approval of ADCs in future trials.

Background: Severe asthma is associated with an increased risk of osteoporosis, largely due to chronic corticosteroid exposure and persistent systemic inflammation. Data from different international registries indicate a significant prevalence of osteoporosis among patients with severe asthma, with large variations attributed to differences in treatment strategies and optimization of care. Aims and Methods: This study aims to assess the prevalence of osteoporosis among patients with severe asthma enrolled in the Severe Asthma Network Italy (SANI) registry who are receiving treatment with monoclonal antibodies (mAbs) and/or long-acting muscarinic antagonists (LAMAs) and compare the characteristics of patients with and without osteoporosis to identify key risk factors contributing to osteoporosis. Results: A total of 1813 patients receiving Step 5 GINA (mAbs, LAMAs) treatment were included in the final analysis, of whom 282 (15.5%) had osteoporosis. Osteoporosis prevalence was significantly higher in women (20.3%) compared to men (8.0%). The prevalence also increased with age (p < 0.001) and with asthma duration (p = 0.008). Patients with osteoporosis exhibited poorer asthma control, lower lung function (FEV1 and FVC), a higher rate of exacerbations, and more frequent chronic oral corticosteroid (OCS) use compared to those without osteoporosis. Nasal polyposis was not significantly associated with osteoporosis in this cohort. Conclusions: Osteoporosis is highly prevalent in individuals with severe asthma, mainly due to chronic corticosteroid exposure and persistent inflammation, and is associated with asthma duration, sex, age, frequent exacerbations, cumulative exposure to OCS, and reduced lung function. Early recognition of osteoporosis risk is essential, and biologic therapies offer a promising strategy to reduce OCS dependence, mitigate adverse effects, and improve long-term outcomes.

Background: The surrogacy of progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancers (NSCLC) is influenced by several clinical-pathological factors. However, potential heterogeneity of PFS surrogacy according to patients’ sex has never been investigated. Methods: RCTs testing ICIs as monotherapy or combined with chemotherapy in patients with advanced NSCLC reporting hazard ratios (HRs) for PFS and OS according to patients’ sex were included. The main objective was to assess sex-based heterogeneity in the trial-level association between PFS (surrogate endpoint) and OS (reference endpoint), overall and in subgroups defined by treatment type (ICIs as monotherapy vs ICIs plus chemotherapy). We used the coefficient of determination (R2) to quantify surrogacy. Results: Twenty RCTs, for a total of 7528 male and 3008 female patients, were included. Overall, the association between OS-HR and PFS-HR was moderate: the R2 from a model adjusted by the type of treatment administered in the experimental arm was 0.69 (95% confidence interval [CI] = 0.34 to 0.88). Sex-disaggregated analysis showed heterogeneity in PFS surrogacy: the association was strong in male patients (adjusted R2 = 0.77; 95% CI = 0.56 to 0.89), but poor in female (adjusted R2 = 0.31, 95% CI = 0.03 to 0.63). Consistent results were obtained in subgroups analyses by treatment type, and in cross-validation analysis. Conclusions: In RCTs testing ICIs alone or combined with chemotherapy in patients with advanced NSCLC, PFS is a robust surrogate endpoint for OS in male patients but not in female.