APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research.

INTRODUCTION: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). METHODS AND OBJECTIVES: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. CONCLUSION: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project.

A case of fatal late vasospasm in a patient with a recurrent, supratentorial rhabdoid primitive neuroectodermal tumor: possible molecular implications.

We report the case of a 44-year-old man who experienced a fatal and untreatable delayed vasospasm after resection of a recurrent temporal IV grade primitive neuroectodermal tumor (PNET). The histological analysis demonstrated a rare rhabdoid variant of the tumor with a diffuse myxoid degeneration; molecular investigations demonstrated an upregulation of IL-1ß and IL-6 expression in the recurrence. We reviewed the pathophysiology of the vasospasm that occurs after tumors resection, and due to the rarity of case, we speculated on the possibility that specific histological and molecular features of the tumor could have contributed to the delayed and fatal complication.

Current role and safety profile of aromatase inhibitors in early breast cancer.

The current adjuvant therapy for breast cancer is in a continous progress; standard therapeutic strategies include the use of chemotherapy, molecular targeted drugs and hormonal agents, according to well-established prognostic and predictive factors. Among the hormonal drugs, for a long period tamoxifen has been the gold standard of adjuvant therapy in postmenopausal women with hormone receptor-positive (HR+) early breast cancer. In the last years an expanding use of aromatase inhibitors occurred in this subset of patients, because the third-generation class of these agents (anastrozole, letrozole and exemestane) showed to be more effective and safe than tamoxifen and are now recommended as the preferred hormonal approach to postmenopausal hormone-sensitive patients, according to national and international guidelines. Treatment choices with these agents include the use of an aromatase inhibitor as an upfront strategy for 5 years, as a sequential approach after 2-3 years of tamoxifen, or as an extended use after the classical 5 years of tamoxifen. The improved efficacy of aromatase inhibitors over tamoxifen has been largely demonstrated in terms of better disease-free survival, reductions in the occurrence of early distant metastasis as well as improvement of overall survival. Moreover, according to the optimal duration of therapy, presently it is not known whether aromatase inhibitor therapy, as tamoxifen, should be limited to 5 years. In terms of safety profile, the side effects of aromatase inhibitors, as compared with selective estrogen receptor modulators, are different, reflecting the specific mechanism of action of these drugs. There is strong evidence that aromatase inhibitors are well tolerated, with a lower incidence of gynecological symptoms (vaginal bleeding, discharge and endometrial neoplasia), venous thromboembolic events and hot flushes than tamoxifen. On the other hand, the use of aromatase inhibitors has been associated with loss of bone density, arthralgia, myalgia, and a negative effect on lipid metabolism and cardiovascular risk. More extensive and mature studies are necessary to well establish the safety of aromatase inhibitors when given to patients with breast cancer for a long time.