Lung neuroendocrine neoplasms (NENs) represent about 20

BACKGROUND:High-grade gastro-entero-pancreatic neoplasms (HG GEP-NENs) can be stratified according to their morphology and Ki-67 values into three prognostic classes: neuroendocrine tumors grade 3 (NETs G3), neuroendocrine carcinomas with Ki-67 < 55% (NECs <55) and NECs with Ki-67 ≥ 55% (NECs ≥55). METHODS:We analyzed a cohort of 49 HG GEP-NENs by targeted Next-Generation Sequencing (TrueSight Oncology 500), RNA-seq, and immunohistochemistry for p53, Rb1, SSTR-2A, and PD-L1. RESULTS:Frequent genomic alterations affected TP53 (26%), APC (20%), KRAS and MEN1 (both 11%) genes. NET G3 were enriched in MEN1 (p = 0.02) mutations, while both NECs groups were enriched in TP53 (p = 0.001), APC (p = 0.002) and KRAS (p = 0.02) mutations and tumors with TMB ≥ 10 muts/Mb (p = 0.01). No differentially expressed (DE) gene was found between NECs <55% and NECs ≥55%, while 1129 DE genes were identified between NET G3 and NECs. A slight enrichment of CD4+ and CD8+ T cells in NECs and of cancer-associated fibroblasts and macrophages (M2-like) in NET G3. Multivariate analysis identified histologic type and Rb1 loss as independent prognostic factors for overall survival. CONCLUSIONS:This study showed that GEP-NET G3 and GEP-NECs exhibit clear genomic and transcriptomic differences, differently from GEP-NECs <55% and GEP-NECs ≥55%, and provided molecular findings with prognostic and potentially predictive value.

688 Background: Internationally avelumab is approved as maintenance therapy for patients (pts) with LA/mUC whose disease did not progress after 1L platinum-based chemotherapy. However, 54% of pts progressed on avelumab. Limited data are available on predictive biomarker of efficacy. Artificial intelligence (AI) methods are being increasingly investigated to generate predictive models applicable in clinical practice. In this study, we developed a set of machine learning (ML) classifiers and survival analysis algorithms using real-world data to predict response and progression free survival (PFS) in LA/mUC patients treated with avelumab. We also applied explainability to the developed algorithms. Methods: We prospectively collected real-world data from 115 pts receiving Avelumab from 2021 to 2022 treated in 20 institutions in Italy (MALVA dataset). In order to predict the efficacy of immunotherapy (IO), 2 different outcomes were studied: Objective Response Rate (ORR) and Progression Free Survival (PFS). The dataset was split between training and test set, with a 80%-20% ratio.The missing values were imputed using a Bayesian Ridge iterative imputer, fitted on the training set. Eight different classifier models were used for ORR: XGBoost (XGB), Logistic Regression (LR), Random Forest (RF), Multilayer Perceptron (MLP), Support Vector Machine (SVM), Adaboost (AB), Extra Trees (ET) and LightGBM (LGBM). Five ML survival analysis models were used to analyse PFS: Cox Proportional Hazards (CPH), Random Survival Forest (RSF), Gradient Boosting (GB), Extra Survival Trees (EST) and Survival Support Vector Machine (SSVM). Finally, SHAP values, an eXplainable AI (XAI) technique, were calculated to evaluate each feature and to explain the predictions. Results: According to clinical expertise, 31 features were selected through a clinical hypothesis. For ORR prediction, the two best performing models were XGB and ET, both without using oversampling. On the test set, XGB achieved a F1 score of 0.77, accuracy of 0.77 and AUC of 0.81, while ET reached F1 score and accuracy of 0.81 and AUC of 0.80. Regarding the prediction of PFS, EST and RSF obtained the best performances with a c-index of 0.71 and 0.72, and Average AUC of 0.75 and 0.76, respectively. According to SHAP, the most important feature for predicting ORR was: ORR after 1 st line CHT, while bone metastases, absolute leukocytes number at baseline and ECOG PS were the most important features for the PFS prediction. Conclusions: Machine learning is useful to predict efficacy in advanced urothelial carcinoma. The explainability models confirmed what have been discovered within the last years of immune-research conferring trustworthiness to the ML models. Further validation of these approaches on larger and external pts cohorts is needed.

Among neuroendocrine neoplasms (NENs), a non-negligible proportion (9–22%) is represented by sufferers of NENs of unknown primary origin (UPO), a poor prognostic group with largely unmet clinical needs. In the absence of standard therapeutic algorithms, current guidelines suggest that the treatment of UPO-NENs should be based on tumor clinical-pathological characteristics, disease burden, and patient conditions. Chemotherapy represents the backbone for the treatment of high-grade poorly differentiated UPO-NENs, usually providing deep but short-lasting responses. Conversely, the spectrum of available systemic therapy options for well-differentiated UPO-NENs may range from somatostatin analogs in indolent low-grade tumors, to peptide receptor radioligand therapy, tyrosine kinase inhibitors (TKIs), or chemotherapy for more aggressive tumors or in case of high disease burden. In recent years, molecular profiling has provided deep insights into the molecular landscape of UPO-NENs, with both diagnostic and therapeutic implications. Although preliminary, interesting activity data have been provided about upfront chemoimmunotherapy, the use of immune checkpoint inhibitors (ICIs), and the combination of ICIs plus TKIs in this setting. Here, we review the literature from the last 30 years to examine the available evidence about the treatment of UPO-NENs, with a particular focus on future perspectives, including the expanding scenario of targeted agents in this setting.

AbstractPurpose: To demonstrate the negative prognostic impact of a panel of genomic alterations (PRESSING-HER2 panel) and lack of HER2 amplification by next-generation sequencing (NGS) in patients with HER2+, RAS wild-type metastatic colorectal cancer receiving dual HER2 blockade. Experimental Design: The PRESSING-HER2 panel of HER2 mutations/rearrangements and RTK/MAPK mutations/amplifications was assessed by NGS. HER2 amplification was confirmed by NGS if copy-number variation (CNV) was ≥ 6. With a case–control design, hypothesizing 30% and 5% PRESSING-HER2 positivity in resistant [progression-free survival (PFS) <4 months and no RECIST response] versus sensitive cohorts, respectively, 35 patients were needed per group. Results: PRESSING-HER2 alterations included HER2 mutations/rearrangements, EGFR amplification, and BRAF mutations and had a prevalence of 27% (9/33) and 3% (1/35) in resistant versus sensitive patients (P = 0.005) and 63% predictive accuracy. Overall, HER2 nonamplified status by NGS had 10% prevalence. Median PFS and overall survival (OS) were worse in PRESSING-HER2+ versus negative (2.2 vs. 5.3 months, P < 0.001; 5.4 vs. 14.9 months, P = 0.001) and in HER2 nonamplified versus amplified (1.6 vs. 5.2 months, P < 0.001; 7.4 vs. 12.4 months, P = 0.157). These results were confirmed in multivariable analyses [PRESSING-HER2 positivity: PFS HR = 3.06, 95% confidence interval (CI), 1.40–6.69, P = 0.005; OS HR = 2.93, 95% CI, 1.32–6.48, P = 0.007]. Combining PRESSING-HER2 and HER2 CNV increased the predictive accuracy to 75%. Conclusions: PRESSING-HER2 panel and HER2 nonamplified status by NGS warrant validation as potential predictive markers in this setting. See related commentary by Raghav et al., p. 260

This table summarizes the different screening sources and the corresponding NGS assays.

Background: Metastatic Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors characterized by high morbidity and limited systemic treatment options, mainly based on radiometabolic treatments or chemotherapy. Based on the preclinical rationale that PGGLs carcinogenesis relies on angiogenesis, treatment with tyrosine kinase inhibitors (TKI) may represent another viable therapeutic option. Methods: We conducted a prospective phase II study in patients with metastatic or unresectable PGGLs. Patients received sunitinib (50 mg daily for 4 weeks, followed by a 2-week rest period) until progressive disease (PD), unacceptable toxicity or consent withdrawal. The primary endpoint was 12-month progression-free survival (PFS) rate; secondary endpoints were safety overall response rate (ORR) according to RECIST 1.1 criteria and overall survival (OS). EudraCT Number: 2011-002632-99. Results: Fifty patients were included. At a median follow-up of 71.7 months (IQR 35.4-100.1), the 1 year-PFS rate was 53.4 % (95 %CI 41.1-69.3) and median PFS was 14.1 months (95 % CI 8.9-25.7). ORR was 15.6 %, the median OS was 49.4 months (95 %CI 21.2-NA), and grade 3 or higher treatment-related adverse events were reported in 34 % patients. No significant correlation was found between specific genetic alterations or genomic clusters and sunitinib efficacy. Conclusion: Sunitinib is an active drug in patients with advanced PGGLs, capable of inducing prolonged disease control with a manageable toxicity profile.

Restricted cubic spline plot showing the association of HER2 CNV and PFS (panel A) and OS (panel B).

Metastatic pheochromocytomas and paragangliomas (PPGLs) are frequently associated with skeletal complications. Primary objective: to describe the frequency of adverse skeletal related events (SREs) in PPGL patients with bone metastases (BMs). Secondary objectives: to 1) identify predictive and prognostic factors for SREs and 2) obtain information on the effectiveness of bone resorption inhibitors in reducing SRE risk and improving outcomes in term of survival and SREs time onset. In this retrospective multicenter, multinational study, 294 PPGL patients were enrolled. SREs occurred in 90 patients (31 %). Fifty-five patients (19 %) had bone fractures, 47 (16 %) had spinal cord compression, and 11 (4 %) had hypercalcemia. Twenty-two patients (7 %) had more than one SRE. Sixty-four patients (22 %) underwent surgery, and 136 (46 %) underwent radiotherapy. SREs occurred a median of 4.4 months after diagnosis of BM (range, 0-246.6 months). Independent factors associated with reduced risk of SREs in multivariable analysis were I-131-MIBG radionuclide therapy (hazard ratio [HR], 0.536 [95 % CI, 0.309-0.932]; P = .027) and absence of liver metastases (HR, 0.638 [95 % CI, 0.410-0.992]; P = .046). The median overall survival duration was 5.3 year. In multivariable analysis, age younger than 48 years at PPGL diagnosis (HR, 0.558 [95 % CI, 0.3877-0.806]; P = .002), absence of liver metastases (HR, 0.618 [95 % CI, 0.396-0.965]; P = .034), treatment with bisphosphonates or denosumab (HR, 0.598 [95 % CI, 0.405-0.884]; P = .010), and MIBG radionuclide therapy (HR, 0.444 [95 % CI, 0.274-0.718]; P = .001) were associated with a reduced risk of death. SREs occur frequently and early in bone-metastatic PPGL patients but do not negatively impact survival. MIBG radionuclide therapy and treatment with bone resorption inhibitors are associated with favorable outcome.

Boxplot for HER2 CNV in resistant vs sensitive patients.

Response to dual HER2 blockade in patients with PRESSING-HER2 alterations.

Abstract In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract. Enrolled patients received lanreotide ATG 120 mg plus oral metformin, up to a maximum dosage of 2550 mg/day. We enrolled 20 patients, of whom 18 (90%) and 2 (10%) had WDNETs of the GI and thoracic tract, respectively. Fourteen patients (70%) were non-diabetic. With a 5% incidence of SAEs, the study met its primary objective of demonstrating treatment safety. With a median follow-up of 39 months (95% CI 28-NE), median PFS was 24 months (95% CI 16-NE), with 12-month and 24-month PFS probability of 75% (95% CI 58–97) and 49% (95% CI 31–77), respectively. We found no statistically significant PFS differences between diabetic and non-diabetic patients. Among exploratory analyses, the presence of tumor genomic alterations in DNA damage pathways was associated with trend towards worse PFS, whereas a precocious reduction of HOMA-IR index and plasma cholesterol concentration showed a trend towards an association with better PFS. In conclusion, metformin plus lanreotide ATG is a safe and well tolerated combination treatment that is associated with promising antitumor activity in both non-diabetic and diabetic patients with WDNETs, and that warrants further investigation in larger clinical trials.

Background: The immune system (innate and adaptive) is influenced by vitamin D3, which affects gene expression and inflammatory pathways. An umbrella review was conducted to evaluate the power and accuracy of data connecting vitamin D3 to the outcomes of COVID-19 infection and to appraise the proof provided by published meta-analyses. Methods: MEDLINE, Embase, and the Cochrane Library were searched from database inception to 31 May 2022. Meta-analyses of prospective or retrospective observational studies and randomized trials were included. Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: From 74 publications, 27 meta-analyses described five associations between vitamin D3 levels and supplementation and COVID-19 outcomes. Low levels of vitamin D3 were significantly associated with severity (highly suggestive evidence; OR = 1.97 [95% CI, 1.55–2.51], p < 0.01; I2 = 77%, p < 0.01) and mortality risk due to COVID-19 disease (OR = 1.83 [95% CI, 1.55–2.16], p < 0.01; I2 = 50%, p < 0.01). Vitamin D3 supplementation, after a diagnosis of COVID-19 infection, was associated with significantly reduced infection severity (e.g., ICU admission) and mortality. Conclusions: This umbrella review of the available evidence suggests that insufficient vitamin D3 may increase COVID-19 infection risk, severity, and mortality, in addition to showing a highly suggestive association between vitamin D3 supplementation and reduced severity and mortality among infected patients.

Background Well-differentiated (WD) neuroendocrine tumors (NETs) are a group of rare neoplasms with limited therapeutic options. Cabozantinib is an inhibitor of multiple tyrosine kinases with a pivotal role in NET pathogenesis, including c-MET and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). LOLA is the first prospective phase II trial aiming to assess the safety and activity of cabozantinib combined with lanreotide in WD NETs of gastroenteropancreatic (GEP), thoracic and of unknown origin. Methods This is a multicenter, open-label, double-cohort, non comparative, non-randomized, three-stage phase II trial. Eligible patients have to meet the following inclusion criteria: diagnosis of advanced or metastatic, progressive, non-functioning WD thoracic NETs, GEP-NETs or NETs of unknown origin with Ki67 ≥ 10%; positive 68 Ga-PET uptake or somatostatin receptor 2 immunohistochemical (IHC) stain; maximum 1 prior systemic regimen for metastatic disease. Two cohorts will be considered: pNETs and carcinoids (typical or atypical lung and thymus NETs, gastro-intestinal NETs or NETs of unknown origin). In stage I, the primary objective is to find the optimal dose of cabozantinib in combination with lanreotide and to evaluate the safety of the combination (percentage of patients experiencing grade 3–5 toxicities according to NCI-CTCAE version 5.0). Starting dose of cabozantinib is 60 mg/day continuously, plus lanreotide 120 mg every 28 days. In stage II and III, co-primary endpoints are safety and overall response rate (ORR) according to RECIST version 1.1. The uninteresting antitumor activity is fixed in ORR ≤ 5%. Secondary endpoints are progression-free survival and overall survival. Exploratory objectives include the assessment of c-MET, AXL and VEGFR2 IHC expression, to identify predictive or prognostic tissue biomarkers. Enrolment started in July 2020, with an expected trial duration of 42 months comprehensive of accrual, treatment and follow-up. Considering a drop-out rate of 5%, the maximum number of enrolled patients will be 69. Discussion Supported by a solid rationale, the trial has the potential to generate milestone data about the synergistic effects of cabozantinib plus lanreotide in a group of NET patients with relatively aggressive disease and limited therapeutic options. Trial registration LOLA is registered at ClinicalTrials.gov (NCT04427787) and EudraCT (2019–004506-10).

Approximately 11% to 14% of subjects with neuroendocrine neoplasms (NENs) have metastatic lesions with unknown primary origin (UPO), with the majority of UPO-NENs found in the small bowel. Herein, we assessed the available literature on UPO-NENs, focusing on clinical presentation and diagnostic techniques to identify the primary site. The identification of the primary tumor is important as it affects the prognosis; however, the clinical presentation can be non-specific in non-functioning forms. In the presence of metastatic disease, the histological sample is fundamental to obtain immunohistochemical markers that might orientate the clinician in the search for the primary tumor through radiology, functional imaging and endoscopic techniques. In summary, multidisciplinary management plays a key role in UPO-NENs, even more than in other NENs. Molecular biology and gene-expression profiling represent areas of great interest which might be developed in the near future for both the diagnosis and the treatment of these neoplasms.

3569 Background: Encorafenib plus cetuximab is a standard option in the treatment of BRAF V600E mut mCRC pts pre-treated with at least one systemic therapy. RNF43 is a negative regulator of WNT pathway. A recent study showed that RNF43 mutation is associated with better outcome among pMMR/MSS BRAF V600E mut mCRC patients treated with TT but not in an independent cohort of pts not treated with TT (Elez et al. Nat Med 2022). However, no comparison is available between TT vs CT as second-line (2L) treatment for pMMR/MSS BRAF V600E mut mCRC according to RNF43 mutational status. Methods: The predictive impact of RNF43 mut was evaluated in a real-life dataset of 126 pMMR/MSS BRAF V600E mut mCRC pts treated with TT (consisting of BRAF inhibitor + anti-EGFR antibody ± MEK inhibitor) vs CT ± target agent as 2L treatment. A cohort of 36 pts receiving TT after 2L was also analyzed. Results: Thirty-one (25%) and 95 (75%) out of 126 pMMR/MSS BRAF V600E mut tumours were RNF43 mut and RNF43 wt, respectively. In the RNF43 mut group 14 (45%) received CT and 17 (55%) TT; in the RNF43 wt group, 56 (59%) and 39 (42%) received CT and TT, respectively. Among RNF43 mut pts, those treated with TT reported longer PFS (7.1 vs 3.0 months, HR: 0.35 95%CI: 0.16-0.76, p = 0.006) and higher ORR (42% vs 0%, p = 0.009) than those receiving CT. On the other hand, no significant difference was observed among RNF43 wt patients in terms of PFS (4.3 vs 3.7 months, HR: 0.69 95% CI: 0.45-1.05, p = 0.080) and ORR (28% vs 16%, p = 0.24). However, no significant interaction between treatment effect and RNF43 mutational status was reported in terms of PFS (p interaction = 0.17) and ORR (p interaction = 0.96). After excluding 36 pts in the CT group that received TT after 2L, no interaction effect was observed also in terms of OS (p interaction = 0.53). However, among RNF43 mut pts, those treated with TT reported longer OS (16.5 vs 10.1 months; HR: 0.34 95% CI: 0.11-1.00, p = 0.049), while no significant difference was observed among RNF43 wt pts (10.6 vs 6.6 months; HR: 0.66 95% CI: 0.39-1.11; p = 0.12). In the group receiving TT after 2L, 9 (25%) out of 36 cases were RNF43 mut and achieved higher ORR (78% vs 26%, p = 0.014) and longer PFS (10.1 vs 4 months; HR: 0.35 95%CI: 0.14-0.88; p = 0.020) and OS (11.7 vs 7 months; HR: 0.35 95%CI: 0.15-0.82; p = 0.012) than RNF43 wt (N = 27). Conclusions: pMMR/MSS BRAF V600E mut mCRC patients achieve benefit from TT vs CT independently of RNF43 mutational status, but a higher magnitude of benefit from TT is observed among those with RNF43 mut tumors. These findings deserve confirmation in past and current randomized trials (i.e. BEACON and BREAKWATER).

684 Background: Preliminary results of the interim analysis of the ARCADIA trial have shown that combining multitargeted receptor tyrosine kinase inhibitor CABO with the checkpoint inhibitor DURVA has promising activity and a manageable safety profile in patients (pts) affected by UC recurred or progressed after failure of at least one line of platinum-based chemotherapy for metastatic disease in a phase II study (NCT03824691). To identify peripheral blood biomarkers potentially associated with clinical response, we carried out a quantitative profiling of innate and adaptive immune subsets from a subset of treated pts. Methods: From 09/2019 and 08/2023 blood samples from 65 pts were collected at baseline and before the third treatment cycle. Absolute cell counts for 29 innate and adaptive immune subsets were determined by multiparametric flow cytometry. Results: In pre-therapy samples a significant higher counts for all CD45+ leukocytes were found in non-responders compared to responders (p=0.0053, Mann Whitney test, n= 27 patients). This was, explained by higher counts for CD16+CD15+ neutrophils (p=0.0005), classical CD14+CD16- (p=0.0119) and CD14++CD16+ intermediate (p=0.0186) monocytes, CD56dim CD16+ NK cells (p=0.0365) and Lin-HLA-DR-/LoCD33+CD14+CD15- M-MDSCs (p=0.0281). At baseline, higher neutrophils counts were associated with worse PFS (p=0.0117, log rank test), while higher eosinophils counts were associated with improved PFS (p=0.0158). Compared to responders, non-responders underwent a significant reduction in post-treatment counts for all CD45+ leukocytes (p=0,0024, Wilcoxon matched pair test), due to reduction of neutrophils (p=0.0068), CD15+CD16- eosinophils (p=0.0068), CD3+ T cells (p=0.0425) CD19+ B cells (p=0.0068), classical monocytes (p=0.0034), activated (HLA-DR+) CD56dim CD16- NK cells (p=0.0068), M-MDSCs (p=0.0161), Lin- HLA-DR-/Lo CD33+ CD14- CD15+ PMN-MDSCs (p=0.001), Lin- HLA-DR+ CD33- pDCs (p=0.0269) and Lin- HLA-DR+ CD33+ mDCs (p=0.0005). Conclusions: These preliminary findings suggest that high baseline counts for granulocytes, monocytes and MDSCs may negatively impact on response in pts treated with CABO+DURVA. Moreover, baseline neutrophils and eosinophils counts show opposite impact on PFS. Grant support: NET-2016-02361632 from Italian Health Ministry to A. Anichini. Clinical trial information: NCT03824691 .

Introduction: The outbreak of COVID-19 poses an unprecedented challenge to global public health. Patients with cancer are at a higher risk during the SARS-CoV-2 pandemic. Patients with lung cancer and COVID-19 were compared to those without cancer and those with other malignancies for the main outcome of this study. The aim of this study was to evaluate the differences in susceptibility, disease severity, and mortality between lung cancer patients and the general population. Methods: Using PRISMA reporting guidelines, we conducted a systematic review and meta-analysis of the published literature. The Cochrane Library database, PubMed, EMBASE, and PubMed Central were comprehensively searched for published papers until 31 May 2022. A pooled risk ratio (OR) with 95% CI was presented as the result of this meta-analysis. Results: We included 29 studies involved 21,257 patients with lung cancer and SARS-CoV-2 infection. Analysis data showed that mortality in patients with lung cancer was significantly higher than that in patients without cancer (HR = 2.00 [95%CI 1.52, 2.63], p < 0.01) or with other malignancies (HR = 1.91 [95%CI 1.53, 2.39], p < 0.01). In addition, we also observed a higher risk of severe infection in terms of life-threatening or required ICU admission/mechanical ventilation for lung cancer patients (HR = 1.47 [95%CI 1.06, 2.03], p = 0.02) than for patients with no cancer or other malignancies. Regarding lung cancer as a risk factor for acquiring SARS-CoV-2 infection, we could not reach statistical significance (hazard ratio [HR] =2.73 [95%CI 0.84, 8.94], p = 0.1). Conclusion: Lung cancer represents an important comorbidity and modifies COVID-19 prognosis in terms of disease severity and mortality. More patients experience severe or even fatal events. Considering their inherent fragility, patients with lung cancer, and generally all oncological populations, should be treated more carefully during the COVID-19 pandemic.

Purpose: Breast cancer (BC) patients’ (pts) management was affected by a global reorganization after Coronavirus disease 2019 (COVID-19). Our multicenter study aimed to assess the impact of COVID-19 on access to diagnosis, staging and treatment for BC pts compared to pre-pandemic. Methods: Medical records of all consecutive newly diagnosed BC pts referred to 6 Italian Institutions between March and December 2020 were assessed. Monthly access rate and temporal intervals between date of symptoms onset, radiological, cytohistological diagnosis and treatment start were analyzed and compared with 2019. Results: A reduction (25%) in newly diagnosed BC was observed compared to 2019 (666 vs 890). New BC pts in 2020 were less likely to be diagnosed with early stage BC (77% vs 83%, p < 0.01), had a worse performance status according to the Eastern Cooperative Oncology Group (ECOG PS) (19.8% had PS > 0 in 2020 vs 16.5% in 2019, p < 0.01) and fewer pts were asymptomatic at diagnosis in 2020 (54% vs 71%,p < 0.01). COVID-19 did not negatively impact in terms of access to diagnosis, staging and treatment. Time intervals between symptom onset and radiological diagnosis, symptom onset and cytohistological diagnosis, cytohistological diagnosis and treatment start were maintained or improved. However, less cases were discussed in multidisciplinary tumor meetings during 2020 (60% vs 73%, p < 0.01). Conclusions: Our data proved an alarming reduction of early stage BC associated with the COVID-19 crisis in 2020. Despite the upheaval generated by the pandemic, our study shed light on the effective performance delivered by Italian Oncology Departments to guarantee diagnostic-therapeutic pathways.

e24119 Background: COVID-19 pandemic led to a reorganization of Health Care System for cancer pts, also because of the application of containment measures. The aim of our study was to investigate the emotional discomfort of pts and their CGs who needed to access the day-hospital to receive treatment during pandemic. Methods: This is a single-institution, prospective, cross-sectional study. From 5 th May to 5 th June 2020 a survey was conducted at a Department of Oncology in the midst of the Italian outbreak. We compared the points of view of both the “players” through 2 different multiple-choice questionnaires enquiring demographic characteristics, changes in emotional status, interpersonal relationships with health professionals (HCPs) and self-perception of treatment outcomes. Results: 625 pts and 254 CGs were enrolled. Female were prevalent (pts:65%, CGs:56%). Pts were generally older than CGs (pts:70% > 60 y, CGs:50.4% 41-60 y; p < 0.001). 50.5% pts had a low education level (EL) while 67.5% CGs had a higher degree. About half of pts (52.8%) reached the hospital with their own CG who lived together in the 58.3% of cases. 52.5% of pts felt more vulnerable to COVID-19 compared to CGs. Differently, CGs did not feel more exposed to infection, although they were involved in taking care or lived together with pts. The EL influenced the risk contagion perception: people with a lower EL were less worried about being infected with SARS-CoV-2. Regardless of the perceived contagion risk, study participants considered the containment measures a valid support to avoid the spread of infection (pts:92%, CGs:89%; p = 0.163) without an excessive loss of time (pts:78%, CGs:88.6%; p = 0.003). A personal emotional change caused by waiting and performing visits/treatments alone was reported more by CGs (66%) than by pts (32.7%; p < 0.001). Specifically, CGs had greater anxiety (58.8%) and fear of not properly managing pts at home (19.8%). The majority of pts (73%) and CGs (62%) thought that the pandemic didn’t influence treatment outcomes. The relationship with HCPs was not negatively affected for both pts (79.6%) and CGs (95%), but about a quarter of pts (25%) and CGs (29%) thought that the attention of HCPs was more focused on COVID-19 than on cancer treatment. Conclusions: The majority of pts felt at higher risk of COVID-19 infection and therefore approved the application of safety standards to help them feel more protected. Good relationships with HCPs contributed to receive treatments without experiencing additional distress. For CGs the main troubles are limitations which don’t allow to fully share the pts' care route and the perceive an impairment in HCPs relationship. Starting from these data, we can better understand the current psychological distress of pts and their families in order to develop potential strategies to support them in this strenuous period of crisis.