The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. A significant increase in fat body mass (mean + 7.2

Background: The combination of encorafenib with cetuximab has become the standard of care in patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC) after a prior systemic therapy. This study aims to describe the efficacy and safety of encorafenib/cetuximab +/- binimetinib in patients with BRAF V600E-mutated mCRC in a real-world setting. Patients and methods: This retrospective study included patients with BRAF V600E-mutated mCRC who received this combination from January 2020 to June 2022 in 30 centers. Results: A total of 201 patients were included, with 55% of women, a median age of 62 years, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) >1 in 20% of cases. The main tumor characteristics were 60% of right-sided primary tumor, 11% of microsatellite instability/mismatch repair deficient phenotype, and liver and peritoneum being the two main metastatic sites (57% and 51%). Encorafenib/cetuximab +/- binimetinib was prescribed in the first, second, third, and beyond third line in 4%, 56%, 29%, and 11%, respectively, of cases, with the encorafenib/cetuximab/binimetinib combination for 21 patients (10%). With encorafenib/cetuximab treatment, 21% of patients experienced grade >= 3 adverse events (AEs), with each type of grade >= 3 AE observed in <5% of patients. The objective response rate was 32.2% and the disease control rate (DCR) was 71.2%. The median progression-free survival (PFS) was 4.5 months [95% confidence interval (CI) 3.9-5.4 months] and the median overall survival (OS) was 9.2 months (95% CI 7.8-10.8 months). In multivariable analysis, factors associated with a shorter PFS were synchronous metastases [hazard ratio (HR) 1.66, P = 0.04] and ECOG-PS >1 (HR 1.88, P = 0.007), and those associated with a shorter OS were the same factors (HR 1.71, P = 0.03 and HR 2.36, P < 0.001, respectively) in addition to treatment beyond the second line (HR 1.74, P = 0.003) and high carcinoembryonic antigen level (HR 1.72, P = 0.003). Conclusion: This real-world study showed that in patients with BRAF V600E-mutated mCRC treated with encorafenib/cetuximab +/- binimetinib, efficacy and safety data confirm those reported in the BEACON registration trial. The main poor prognostic factors for this treatment are synchronous metastases and ECOG-PS >1.

Women with early breast cancer (EBC) receiving adjuvant aromatase inhibitors (AIs) are frequently given denosumab (Den) with the aim to both reducing fracture risk and preventing disease recurrence. However, a proportion of these patients still experience fragility fractures despite Den, and risk factors in women treated with upfront AIs and Den have never been explored. Dual-X-ray absorptiometry (DXA) at baseline conditions and after 18 months was performed in 237 consecutive patients undergoing adjuvant therapy with AIs and Den (60 mg subcutaneously every 6 months), recruited at the Breast Unit of the ASST-Spedali Civili of Brescia. The following baseline parameters were evaluated to predict the risk of vertebral fracture (VF) as assessed by a morphometric approach on DXA images: age, body mass index (BMI), history of previous fractures, family history of fractures, smoking, alcohol consumption, FRAX score, DXA-derived bone mineral density (BMD), trabecular bone score (TBS), percentage fat body mass (%FBM), lean body mass (LBM), appendicular mass index (ALMI). Seventeen out of 237 (7%) reported incident VFs after 18 months of AIs therapy. At the univariate analysis, incident VFs were significantly associated with high FRAX score (Odd Ratio [OR]: 3.786, 95% Confidence interval [CI]: 1.039-13.790), previous VFs (OR: 3.217, 95% CI: 1.185-8.736), high %FBM (OR 5.174, 95% CI: 1.418-18.873, p=0.013), high android fat (OR 9.580, 95% CI: 1.174-78.209, p=0.035) and low ALMI/FBM ratio (OR 0.252, 95% CI: 0.078-0.818, p=0.022). Only high %FBM was independently associated to incident VFs at multivariate analysis. FBM is an independent risk factor for VFs in EBC patients treated with adjuvant AIs and Den. A supervised physical activity aiming at avoiding obesity and potentiating LBM could synergize with Den in preventing AI-induced bone fragility.

CDK4/6 inhibitors (CDK4/6-i) combined with endocrine therapy (ET) have become the standard of care for ER-positive HER2-negative metastatic breast cancer (mBC) and have significantly improved clinical outcomes. In long-term survivors, bone health is a crucial issue. The risk of fragility fractures associated to ET is well established. Preclinical data suggest that CDK4/6-i could have an effect on the bone microenvironment, however no clinical data are available. The aim of this study is to evaluate vertebral fractures (VFs) progression in mBC patients (pts) treated with CDK4/6-i combined with ET. A series of 211 ER-positive HER2-negative mBC pts treated with CDK4/6-i combined with ET and referred to Medical Oncology and Breast Unit of ASST Spedali Civili, Brescia, from 2017 to 2023 were enrolled. VFs were evaluated through CT scan at baseline and at subsequent CT restaging and were classified as mild, moderate and severe based on Genant classification. All pts were female, with a median age of 55.5 years (32-79). CDK4/6-i were administered as first, second and third line of treatment in 113 (53.6%), 65 (30.8%) and 6 (2.9%) pts, respectively. ETs were aromatase inhibitor and fulvestrant in 104 (49.3%) and 107 (50.7%) pts, respectively. At baseline, 141 patients (66.8%) had bone metastases. 102 (48.3%) pts were treated with bone-targeted agents (BTAs). VFs in healthy bone were detected in 22 (10.4%) pts at baseline and in 37 (17.5%) pts after a mFU of 24 months (p<0.001), with 21 (10.1%) pts experiencing VFs progression, defined as the onset of a new VF of the worsening of pre-existing VFs. Among pts receiving BTAs, VFs in healthy bone were detected in 6 (5.9%) pts at baseline and in 16 (15.7%) pts after a mFU of 24 months (p = 0.006). Correlations between fracture risk factors and VFs progression as well as the comparison between patients receiving and patients not receiving BTAs will be presented at the meeting. These data suggest a detrimental effect of CDK4/6-i and ET combination on bone health. Studies with a prospective design, a control arm with ET alone and longer follow-up are needed to better explore this issue.

Purpose Brain metastases rarely complicate the natural history of patients with adrenocortical carcinoma (ACC). No information is available regarding the life expectancy and efficacy of treatments in ACC patients with brain involvement. Methods A pooled analysis was performed by searching on PubMed and using the keywords: “brain metastases in adrenocortical carcinoma”, and “leptomeningeal metastases in adrenocortical carcinoma”. Four patients diagnosed at Spedali Civili Hospital in Brescia were added to the analysis. Data concerning demographic, disease characteristics, adopted treatments and patient prognosis were collected. Results A total of 27 patients (18 adults and 9 children) were included in this study, 22 of them had an adequate follow-up. Brain metastases occurred late in the natural history of adult patients but not in that of children. Surgery plus/minus radiation therapy was the treatment of choice. Adult patients with brain metastases had a poor prognosis with a median progression-free survival (PFS) and overall survival (OS) of 2 and 7 months, respectively. Median PFS and OS were not attained in children. Conclusion Brain metastases in ACC patients are rare and are associated with poor prognosis, particularly in adults. Surgery plus/minus radiotherapy is the only therapeutic approach that can offer patients a chance to obtain durable local disease control.

BACKGROUND:Immune-related adverse events (irAEs) are frequently reported during immune checkpoint inhibitor (ICI) therapy and are associated with long-term outcomes. It is unknown if the irAE occurrence is a valid surrogate of ICIs' efficacy. METHODS:We identified articles reporting the results of randomized trials of experimental ICI therapy in solid tumors with a systematic search. The control arms could be placebo, cytotoxic/targeted therapy, or ICI therapy. We extracted the hazard ratios for overall survival (OS) with the number of OS events per arm and the number and percentages of overall and specific irAEs of grade 1-2 and grade 3-4 per arm. We estimated the treatment effect on the potential surrogate outcome with the odds ratio of the irAE rate between the experimental and the control arm. The statistical analysis consisted of weighted linear regression on a logarithmic scale between treatment effects on irAE rate and treatment effects on OS. RESULTS:Sixty-two randomized trials were included for a total of 79 contrasts and 42 247 patients. The analyses found no significant association between the treatment effects for overall grade 1-2 or grade 3-4 irAE rates or specific (skin, gastrointestinal, endocrine) irAE rates. In the non-small-cell lung cancer (NSCLC) trial subset, we observed a negative association between treatment effects on overall grade 1-2 irAEs and treatment effects on OS in studies with patients selected for programmed death-ligand 1 expression (R2 = 0.55; 95% confidence interval 0.20-0.95; R = -0.69). In the melanoma trial subset, a negative association was shown between treatment effects on gastrointestinal grade 3-4 irAEs and treatment effects on OS in trials without an ICI-based control arm (R2 = 0.77; 95% confidence interval 0.24-0.99; R = -0.89). CONCLUSIONS:We found low-strength correlations between the ICI therapy effects on overall or specific irAE rates and the treatment effects on OS in several cancer types.

Aromatase inhibitors (AIs) represents the standard adjuvant therapy of postmenopausal early breast cancer (EBC) survivors. AIs reduce estrogen and increase androgen levels through inhibition of aromatase enzyme, with possible consequent alterations in body composition (BC). The primary aim of the current study was to examine the impact of nutrition education intervention on BC in EBC patients (pts) treated with AIs. This is a retrospective, two-cohort single-center study. 194 EBC pts referred to the Oncology Department and Breast Unit of ASST Spedali Civili Brescia were enrolled (from 2017 to 2019): 97 patients received a nutrition education intervention by a trained dietician (cohort A) while 97 did not (cohort B). BC was measured by using Dual-Energy X-ray Absorptiometry (DEXA) scan at baseline and after 18 months of AI therapy. The following data were also collected through validated questionnaires: dietary habits with food frequency questionnaire (FFQ), adherence to a Mediterranean diet with PREDIMED questionnaire, physical activity with IPAQ questionnaire, WCRF/AICR diet score was also calculated. Cohorts A compared to the cohorts B pts modified their diet through a reduction in consumption of animal fat, red meat, processed meat, added sugar, bread, cereals, and a rise in fruit and vegetables consumption. Moreover, cohort A pts were more adherent to the Mediterranean diet (PREDIMED score: 8.7 vs 7.2; p<0.001) and to the WCRF's recommendations (WCRF score: 4.4 vs 3.4; p<0.001), increasing slightly physical activity. A significant increase in body weight (65.2 vs 66.4, p<0.001) and BMI (24.8 vs 25.3, p<0.001) was observed only in cohort B. Regardless changing in dietary habits, an increase in adipose tissue and a reduction in lean body mass was observed in both cohorts at 18 months. A significant change in BC with loss of lean mass and an increase of fat body mass was observed during adjuvant AI-therapy despite the nutrition education intervention adopted in cohort A. These findings indicate that a diet, without prescription of tailored physical activity, is not sufficient to prevent change in BC during AI therapies.

CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) represent the standard of care for HR-positive, HER2-negative metastatic breast cancer (mBC). ET increases the risk of bone fracture; moreover, it has been suggested that CDK6 plays a critical role in controlling osteoblast, osteoclast, and chondrocyte differentiation. The possible impact of ET combined with CDK4/6i on bone health has not already been explored. The main aim of the current study is to evaluate the proportion and the evolution of vertebral fractures (VFs) in mBC HR+ patients (pts) treated with ET combined with CDK4/6i. We retrospectively evaluated a series of 170 mBC HR+ treated with combination of CDK4/6i + ET at Medical Oncology and Breast Unit of ASST Spedali Civili, Brescia, from 2017 to 2020. VFs were evaluated through CT scan at baseline and at subsequent restaging CT and classified in mild, moderate, and severe based on Genant classification. Patients were all female, with a median age of 64 years (38-81). Endocrine treatments were Aromatase Inhibitor (AI) and fulvestrant in 44 and 66 % of pts respectively. CDKi treatments administered were palbocilib, ribociclib, and abemaciclib in 61.2, 22.9, and 15,9% of cases respectively. At baseline, 60.0% of pts had visceral metastases, 54.7% had bone metastases and 44.7% were receiving bone modified agents (BMA). More than half of pts experienced partial response as best response to CDK4/6i treatment and almost all (90%) had clinical benefit. VFs were detected at baseline in 22.9% of cases and after a median follow-up (mfu) of 27 months in 37.1% of pts. Nearly 20% of pts had a worsening of VFs in terms of new VFs or worsening of pre-existing VFs. Correlation between fracture risk factors with the onset of new or worsening of pre-existing VFs as well as the interaction with BMA will be present at the meeting. These preliminary data suggest a detrimental effect of the combination of CDK4/6i and ET on bone health after a mfu of 27 months. To our knowledge, this is the first study analyzing the impact of CDK4/6i on bone health. Studies with longer follow-up are needed to better explore this issue.

Treatment of RM NPC in non-endemic areas suffers from the lack of prospective trials. We conducted a retrospective multicentre observational study in non-endemic areas in pre-immunotherapy era. Clinical data of 1230 patients (pts) from 11 countries with diagnosis of NPC between 2004 and 2018 were collected in a web-based platform (minimum follow up 12 months). Of these, 454 (36.9%) had RM disease. Survival curves were obtained using Kaplan-Meier method and compared with the log-rank test. We used Cox proportional hazards models to test prognostic factors for death and disease progression. Fifty-eight (13%) pts had metastasis at diagnosis, while 396 (87%) pts relapsed after curative treatment, with a median time to progression (TTP) of 16 months (range 2-236). The table depicts 3-yr PFS and OS in pts subgroups. Patients with loco-regional relapse had a better prognosis (HR 0.48 IC 0.36-0.64). At cox multivariate analysis, younger pts (< 50 years) had a better outcome (HR 0.97 IC 0.95-0.99) as well as who underwent radical treatment as surgery (HR 0.33 IC 0.17-0.66) and/or radiotherapy (HR 0.52 IC 0.28-0.95). RM pts treated with systemic agents received up to 5 lines of chemotherapy (median 3) and the most frequently adopted schedules were platinum-based, in first and second line with an ORR of 68% and 52%, respectively. After starting a first-line chemotherapy 3-yr OS was 34%.Table: 664PSurvivalPts subgroups3-yr PFS3-yr OSAny site of relapse22%44%Loco-regional relapse exclusively27%59%Metastatic relapse exclusively18%31%Loco-regional & metastatic relapse10%32% Open table in a new tab In non-endemic setting, less than half of the pts with RM NPC are alive at 3 years. Pts treated with surgery and/or radiation for loco-regional relapses show better long-term outcome. Response rate to systemic chemotherapy is quite high and pts may receive sequential treatments, however only a limited group of them obtaining long-term survival. The current data represent the large dataset of RM NPC in non-endemic settings, and they could be considered the benchmark to be compared with new treatment approaches also comprising immunotherapy.