Precision oncology implementation in a regional-based health care system: A professional consensus to define the pathway.

Objective: Precision Oncology requires deep changes in organizational settings but little evidence has been identified about the best strategy to guarantee the delivery of this innovation to patients. In the Italian health care system, high heterogeneity could jeopardize equal access opportunity for patients. Following a consensus method, we aim to define shared solutions to address these issues in clinical practice.

Treatment of unresectable stage III non-small cell lung cancer for patients who are under-represented in clinical trials.

Concurrent chemoradiotherapy (cCRT) followed by one year of consolidation durvalumab is the current standard-of-care for patients with unresectable stage III non-small cell lung cancer (NSCLC), of good functional status. However, cCRT and consolidation durvalumab may be challenging to administer for selected patient populations underrepresented or even excluded in clinical trials: older and/or frail patients; those with cardiovascular or respiratory comorbidities in which treatment-related adverse events may be higher, and patients with pre-existing autoimmune disorders for whom immunotherapy use is controversial. In this narrative review, we discuss the current evidence, challenges, ongoing clinical trials and potential future treatment scenarios in relevant subgroups of patients with locally advanced NSCLC, who are underrepresented in clinical trials.

Multidisciplinary management of immunotherapy-related adverse events in solid tumors: An inter-institutional and telemedicine-based working team.

Background: Although immune checkpoint inhibitors (ICIs) show a more favorable toxicity profile than classical cytotoxic drugs, their mechanism of action is responsible for peculiar new toxicities. There is an urgent need for a multidisciplinary approach to advice on how to manage organ-specific toxicities.

Methods: Our project aims to integrate the practices of two different hospitals into a single Italian regional collaborative model to treat immune-related adverse events (irAEs).

Anti-tumor activity of all-trans retinoic acid in gastric-cancer: gene-networks and molecular mechanisms.

Background: Gastric-cancer is a heterogeneous type of neoplastic disease and it lacks appropriate therapeutic options. There is an urgent need for the development of innovative pharmacological strategies, particularly in consideration of the potential stratified/personalized treatment of this tumor. All-Trans Retinoic-acid (ATRA) is one of the active metabolites of vitamin-A.

Implementation of Precision Oncology in the National Healthcare System: A Statement Proposal Endorsed by Italian Scientific Societies.

Purpose: Precision oncology (PO) promises positive results for patients. To date, in Italy, the effort to implement PO has been made autonomously by regional health institutions in a top-down fashion. This approach is not very efficient and jeopardizes patients' equal access to PO.

Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas.

Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application.

Estimating survival in patients with melanoma brain metastases: prognostic value of lactate dehydrogenase.

Patients with melanoma brain metastases (MBM) have poor prognosis, albeit advances in locoregional and systemic treatments. The melanoma-specific Graded Prognostic Assessment (GPA) effectively stratifies survival for patients with MBM. Nevertheless, lactate dehydrogenase (LDH), a well known prognostic factor for patients with melanoma, is not represented in the GPA scores and might add prognostic information for patients with MBM.

Current practice of genomic profiling of patients with advanced solid tumours in Italy: the Italian Register of Actionable Mutations (RATIONAL) study.

Background: The Italian Register of Actionable Mutations (RATIONAL) is a multicentric, observational study collecting next-generation sequencing (NGS)-based tumour profiling data of patients with advanced solid tumours.

Methods: The study enrols patients who had available an NGS-based tumour profiling (Pathway-A) or undergo comprehensive genomic profiling (CGP) with FoundationOne CDx assays within the trial (Pathway-B). The primary endpoint was the rate of actionable mutations identified.

Preoperative treatments in borderline resectable and locally advanced pancreatic cancer: Current evidence and new perspectives.

Surgery is the only curative treatment for non-metastatic pancreatic adenocarcinoma, but less than 20 % of patients present a resectable disease at diagnosis. Treatment strategies and disease definition for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) vary in the different cancer centres. Preoperative chemotherapy (CT) is the standard of care for both BRPC and LAPC patients, however literature data are still controversial concerning the type, dose and duration of the different CT regimens, as well as regarding the integration of radiotherapy (RT) or chemoradiation (CRT) in the therapeutic algorithm.

Implementation of Precision Oncology in Clinical Practice: Results of a National Survey for Health Care Professionals.

Background: Two main aspects lead the implementation of precision oncology into clinical practice: the adoption of extended genome sequencing technologies and the institution of the Molecular Tumor Boards (MTBs). CIPOMO (Italian Association of Heads of Oncology Department) promoted a national survey across top health care professionals to gain an understanding of the current state of precision oncology in Italy.

Methods: Nineteen questions were sent via the SurveyMonkey platform to 169 heads of oncology departments.

Radiation Recall Pneumonitis Anticipates Bilateral Immune-Induced Pneumonitis in Non-Small Cell Lung Cancer.

Radiation recall pneumonitis (RRP) is a rare inflammatory reaction that occurs in previously irradiated fields, and it may be caused by various triggering agents. Immunotherapy has been reported to potentially be one of these triggers. However, precise mechanisms and specific treatments have not been explored yet due to a lack of data in this setting.

The SAFFO Study: Sex-Related Prognostic Role and Cut-Off Definition of Monocyte-to-Lymphocyte Ratio (MLR) in Metastatic Colorectal Cancer.

Background: Emerging data suggest that gender-related immune system composition affects both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC patients treated from 2009 to 2018 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy.

CDK4/6 Inhibitors as Upfront Treatment in a Patient with Breast Cancer Presenting with a Clinical Critic Situation: A Case Report and Review of the Literature.

CDK4/6 inhibitors have revolutionized the treatment algorithm of luminal metastatic breast cancer, becoming the recommended first-line therapy in association with endocrine therapy. However, due to its theoretically greater and more rapid tumor shrinkage, the upfront use of chemotherapy is considered in some clinical situations like visceral crisis. At the state of the art level, a paucity of data is available about the use of CDK4/6 inhibitors in patients presenting with visceral crisis or with life-threatening conditions since this population was historically excluded from clinical trials.

Rare and Insidious Toxicities from New Combination Therapies in Metastatic Renal Cell Cancer: Lessons Learned from Real-Practice.

The advent of immune checkpoint inhibitors in combination with multitarget tyrosine kinase inhibitors has become a standard first-line treatment for metastatic renal cell cancer. Along with survival improvement, new toxicities have emerged. Such adverse events are still complex to be managed and some of them are rare and could be insidious or even fatal.

Non-small cell lung cancer harboring EGFR G724S mutation and exon 19 deletion responded to afatinib monotherapy after multiple lines of target therapies.

Epidermal growth factor receptor (EGFR) G724S mutation represents a resistance mechanism to first- and third-generation EGFR tyrosine kinase inhibitors. Limited data are available regarding the efficacy of afatinib in patients with non-small cell lung cancer (NSCLC) harboring G724S mutation, particularly after osimertinib. A patient diagnosed with advanced EGFR-mutated (exon 19 deletion) NSCLC after several lines of treatment - gefitinib, osimertinib, heat shock protein inhibitors and chemotherapy-developed EGFR G724S mutation retaining the exon 19 deletion.

Immunotherapy in NSCLC Patients with Brain Metastases.

Approximately 40% of unselected non-small cell lung cancer (NSCLC) patients develop brain metastases (BMs) during their disease, with considerable morbidity and mortality. The management of BMs in patients with NSCLC is a clinical challenge and requires a multidisciplinary approach to gain effective intracranial disease control. Over the last decade, immune checkpoint inhibitors (ICIs) have emerged as a game-changer in the treatment landscape of advanced NSCLC, with significant improvements in survival outcomes, although patients with BMs are mostly underrepresented in randomized clinical trials.

Multidisciplinary Approach to Patients With Metastatic Spinal Cord Compression: A Diagnostic Therapeutic Algorithm to Improve the Neurological Outcome.

Introduction: The morbidity associated with metastatic spinal disease is significant because of spinal cord and/or nerve root compression. The purpose of this paper is to define a diagnostic-therapeutic path for patients with vertebral metastases and from this path to build an algorithm to reduce the devastating consequences of spinal cord compression.

Materials And Methods: The algorithm is born from the experience of a primary care center.

Multidisciplinary Team Meeting Proposal and Final Therapeutic Choice in Early Breast Cancer: Is There an Agreement?

Background: A multidisciplinary team meeting (MDM) approach in breast cancer (BC) management is a standard of care. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early BC. The purpose of this study was to define whether there was an agreement between the planned program (i.

Detection of SARS-CoV-2 infection prevalence in 860 cancer patients with a combined screening procedure including triage, molecular nasopharyngeal swabs and rapid serological test. A report from the first epidemic wave.

Introduction: Even if now we have available the weapon of vaccination against SARS-CoV-2, the patients with cancer remains a very frail population in which frequently the immunologic response to vaccination may be impaired. In this setting, the SARS-CoV-2 infection screening retains a great value. However, there are still limited data on the feasibility and efficacy of combined screening procedures to assess the prevalence of SARS-CoV-2 infection (including asymptomatic cases) in cancer outpatients undergoing antineoplastic therapy.

Drug Holidays and Overall Survival of Patients with Metastatic Colorectal Cancer.

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS).

Impact of innovation in oncology: more questions than answers.

Oncology is going through the fastest innovation period in the history of medicine and a growing number of patients improve or experience increased chances of survival. The declining death rate, starting from 1991, resulted in 2.9 million deaths avoided in the United States so far.

First- and second-line treatment strategies for hormone-receptor (HR)-positive HER2-negative metastatic breast cancer: A real-world study.

Background: Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L.

Materials And Methods: 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy.

Management of patients with cancer during the COVID-19 pandemic: The Italian perspective on the second wave.

The novel coronavirus disease 2019 (COVID-19) pandemic has been an overwhelming challenge for worldwide health systems. Since the beginning of year 2020, COVID-19 has represented a potential harm for cancer patients and has often hindered oncology care. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis.

Feasibility and Predictive Performance of a Triage System for Patients with Cancer During the COVID-19 Pandemic.

Background: Triage procedures have been implemented to limit hospital access and minimize infection risk among patients with cancer during the coronavirus disease (COVID-19) outbreak. In the absence of prospective evidence, we aimed to evaluate the predictive performance of a triage system in the oncological setting.

Materials And Methods: This retrospective cohort study analyzes hospital admissions to the oncology and hematology department of Udine, Italy, during the COVID-19 pandemic (March 30 to April 30, 2020).