Table1_Risk of cardiovascular toxicity with combination of immune-checkpoint inhibitors and angiogenesis inhibitors: a meta-analysis.docx

IntroductionCombinations of immune checkpoint inhibitors (ICIs) and angiogenesis inhibitors (AIs) have been investigated for the treatment of several tumor types. Both ICIs and AIs may lead to cardiovascular adverse events, and their combination may potentially increase the risk for cardiovascular toxicity. In the present meta-analysis, we aim to assess the cardiovascular toxicity of ICIs plus AIs vs. AIs alone. Secondary objectives are non-cardiovascular adverse events and efficacy.MethodsSystematic review was performed according to PRISMA statement. Phase II and III randomized clinical trials were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts, from inception to June 2022. The pooled risks for overall response rate (ORR), 1-year progression-free survival (PFS), adverse events (AEs), immune-related AEs, (irAEs), hypertension, and vascular events defined as stroke, myocardial infarction and pulmonary embolisms, were calculated.ResultsIn terms of cardiovascular toxicity, we found higher risk for severe hypertension among patients treated with ICIs plus AIs as compared with those receiving AIs (OR 1.24, 95% CI: 1.01–1.53), but no significant difference was found for any-grade hypertension, and for vascular events. There was also no difference in terms of overall AEs, whereas the incidence of irAEs was increased in the ICIs plus AIs arm, as expected. In terms of efficacy, ICIs plus AIs achieved better ORR (OR 2.25, 95% CI: 1.70–2.97) and PFS (HR 0.49, 95% CI: 0.39–0.63) as compared to AIs alone.ConclusionThe addition of ICIs to AIs significantly increased the risk of high-grade hypertension, but not that of acute vascular events.</p

DataSheet_1_The predictive and prognostic role of metabolic and volume-based parameters of positron emission tomography/computed tomography as non-invasive dynamic biological markers in early breast cancer treated with preoperative systemic therapy.pdf

IntroductionThe role of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in early breast cancer treated with preoperative systemic therapy (PST) is not yet established in clinical practice. PET parameters have aroused great interest in the recent years, as non-invasive dynamic biological markers for predicting response to PST.MethodsIn this retrospective study, we included 141 patients with stage II-III breast cancer who underwent surgery after PST. Using ROC analysis, we set optimal cutoff of FDG-PET/CT parameters predictive for pathological complete response (pCR). We investigated the correlation between FDG-PET/CT parameters and pCR, median disease-free survival (DFS), and median overall survival (mOS).ResultsAt multivariable analysis, baseline SUVmax (high vs low: OR 9.00, CI 1.85 – 61.9, p=0.012) and Delta SUVmax (high vs low: OR 9.64, CI 1.84, 69.2, p=0.012) were significantly associated with pCR rates. Interestingly, we found that a combined analysis of the metabolic parameter Delta SUVmax with the volume-based parameter Delta MTV, may help to identify patients with pCR, especially in the subgroup of hormone receptor positive breast cancer. Delta SUVmax was also an independent predictive marker for both mDFS (high vs low: HR 0.17, 95%CI 0.05-0.58, p=0.004) and mOS (high vs. low: HR 0.19, 95%CI 0.04-0.95, p=0.029).DiscussionOur results suggest that Delta SUVmax may predict survival of early BC patients treated with PST.</p

Characteristics of patients.

<p>Characteristics of patients.</p

Overall survival.

<p>Kaplan Meier estimates of overall survival evaluated from the date of lapatinib-based therapy initiation in 132 patients according to PFS >7 months (solid line) or PFS ≤7 months (dashed line). Median overall survival is 36 months (95% C.I. 9–21 months) and 15 months (19–53 months), respectively (p<0.001).</p

Multivariate analysis for Progression-free survival (PFS) and Overall Survival (OS) from the start of lapatinib-based therapy.

<p>Multivariate analysis for Progression-free survival (PFS) and Overall Survival (OS) from the start of lapatinib-based therapy.</p

Local-regional treatments.

<p>AST: adjuvant systemic therapy</p><p>Local-regional treatments.</p

Adjuvant systemic therapies.

<p>AST: adjuvant systemic therapy; CT: chemotherapy; HT: hormone therapy</p><p>Adjuvant systemic therapies.</p

Clinicopathologic characteristics and univariate analysis.

<p>LVI: lymphovascular invasion; HR: hormone receptor; AST: adjuvant systemic therapy; ER: estrogen receptor; PgR: progesteron receptor</p><p>*p-value according to Kruskal-Wallis, Chi square test or Fisher’s exact test, as appropriate</p><p>Clinicopathologic characteristics and univariate analysis.</p

A. Disease-free survival according to treatment group. Fig 1A shows Kaplan Meier’s disease-free survival curves according to treatment group. B. Disease-free survival according to stage. Fig 1B shows Kaplan Meier’s disease-free survival curves according to stage; the analysis was performed on 301 patients, since data on stage were missing for 2 patients.

<p>A. Disease-free survival according to treatment group. Fig 1A shows Kaplan Meier’s disease-free survival curves according to treatment group. B. Disease-free survival according to stage. Fig 1B shows Kaplan Meier’s disease-free survival curves according to stage; the analysis was performed on 301 patients, since data on stage were missing for 2 patients.</p