The impact of COVID-19 on radiological findings in patients accessing the emergency department: a multicentric study

The aim of this multicentric study is to illustrate how the COVID-19 pandemic lockdown affected the workload and outcomes of radiological examinations in emergency radiology

Endocrine-responsive lobular carcinoma of the breast: features associated with risk of late distant recurrence

BACKGROUND: Invasive lobular carcinomas (ILCs) account for 10-15% of all breast cancers. They are characterized by an elevated endocrine responsiveness and by a long lasting risk of relapse over time. Here we report for the first time an analysis of clinical and pathological features associated with the risk of late distant recurrence in ILCs. PATIENTS AND METHODS: We retrospectively analyzed all consecutive patients with hormone receptor-positive ILC operated at the European Institute of Oncology (EIO) between June 1994 and December 2010 and scheduled to receive at least 5\u2009years of endocrine treatment. The aim was to identify clinical and pathological variables that provide prognostic information in the period beginning 5\u2009years after definitive surgery. The cumulative incidence of distant metastases (CI-DM) from 5\u2009years after surgery was the prospectively defined primary endpoint. RESULTS: One thousand eight hundred seventy-two patients fulfilled the inclusion criteria. The median follow-up was 8.7\u2009years. Increased tumor size and positive nodal status were significantly associated with higher risk of late distant recurrence, but nodal status had a significant lower prognostic value in late follow-up period (DM-HR, 3.21; 95% CI, 2.06-5.01) as compared with the first 5\u2009years of follow-up (DM-HR, 9.55; 95% CI, 5.64-16.2; heterogeneity p value 0.002). Elevated Ki-67 labeling index (LI) retained a significant and independent prognostic value even after the first 5\u2009years from surgery (DM-HR, 1.81; 95% CI 1.19-2.75), and it also stratified the prognosis of ILC patients subgrouped according to lymph node status. A combined score, obtained integrating the previously validated Clinical Treatment Score post 5\u2009years (CTS5) and Ki-67 LI, had a strong association with the risk of late distant recurrence of ILCs. CONCLUSION: We identified factors associated with the risk of late distant recurrence in ER-positive ILCs and developed a simple prognostic score, based on data that are readily available, which warrants further validation

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer

Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triple-negative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients

How the workload and outcome of imaging examinations changed during the covid-19 pandemic lockdown

Summary. Background: On March 9th, 2020, the Italian government decided to go into lockdown due to the COVID-19 pandemic, which led to changes in the workflow of radiological examinations. Aims: Aim of the study is to illustrate how the workload and outcome of radiological exams changed in a community hospital during the pandemic. Methods and Material: The exams performed in the radiology department from March 9th to March 29th, 2020 were retrospectively reviewed and compared to the exams conducted during the same timeperiod in 2019. Only exams coming from the emergency department (ED) were included. Two radiologists defined the cases as positive or negative findings, based on independent blind readings of the imaging studies. Categorical measurements are presented as frequency and percentages, and p-values are calculated using the Chi-squared test. Results and Conclusions: There was a significant reduction in the amount of exams performed in 2020: there were 143 (93|65% male, 60.7±21.5 years) patients who underwent radiological examinations from the ED vs. 485 (255|53% male, 51.2±24.8 years) in 2019. Furthermore, the total number of ED exams dropped from 699 (2019) to 215 (2020). However, the percentage of patients with a positive result was significantly higher in 2020 (69|48%) compared to 2019 (151|31%) (p<.001). The reduction of emergency radiological examinations might be a result of the movement restrictions enforced during the lockdown, and possible fear of the hospital as a contagious place. This translated to a relative increase of positive cases as only patients with very serious conditions were accessing the ED. (www.actabiomedica.it)

Targeted-gene sequencing to catch triple negative breast cancer heterogeneity before and after neoadjuvant chemotherapy

Triple negative breast cancer (TNBC) patients not attaining pathological Complete Response (pCR) after neo-adjuvant chemotherapy (NAC) have poor prognosis. We characterized 19 patients for somatic mutations in primary tumor biopsy and residual disease (RD) at surgery by 409 cancer-related gene sequencing (IonAmpliSeqTM Comprehensive Cancer Panel). A median of four (range 1–66) genes was mutated in each primary tumor biopsy, and the most common mutated gene was TP53 followed by a long tail of low frequency mutations. There were no recurrent mutations significantly associated with pCR. However, half of patients with RD had primary tumor biopsy with mutations in genes related to the immune system compared with none of those achieving pCR. Overall, the number of mutations showed a downward trend in post-as compared to pre-NAC samples. PIK3CA was the most common altered gene after NAC. The mutational profile of TNBC during treatment as inferred from patterns of mutant allele frequencies in matched pre-and post-NAC samples showed that RD harbored alterations of cell cycle progression, PI3K/Akt/mTOR, and EGFR tyrosine kinase inhibitor-resistance pathways. Our findings support the use of targeted-gene sequencing for TNBC therapeutic development, as patients without pCR may present mutations of immune-related pathways in their primary tumor biopsy, or actionable targets in the RD