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The letters addressed by Felice Giordano to Quintino Sella stretch across about 37 years, from 1847 to 1884. The original correspondence is kept at the Fondazione Sella in Biella and its publication is curated by a project promoted by the Centro Studi di Storia dell'Università di Torino. We transcribed and commented these letters, a lengthy work we have split into three parts because of the size and complexity of these documents which reflect Giordano’s multiform and hyperactive living, technical skills, and commitments. A first group of 81 letters and a second group of 72 letters were published. The third and final part of the correspondence is presented in this article and consists of 77 letters from 1877 to 1884. From 1877 Giordano is charged with heavy tasks mainly for the activity and problems of the R. Mining Corps, the Geological Service and the launch of the “great enterprise”: a new Geological Map of Italy, obeying the standards suggested by Giordano himself (1860) and codified by Sella in his famous memoir of 1861. This is an intriguing story characterized by competition until the final victory of Sella, Giordano and the Corps of mining engineers against Antonio Stoppani and his pupil Torquato Taramelli, both supporters of an independent Geological Institute lead by the university world. In this third part of the correspondence, we find the first evidence of a crisis of relations between the two friends of a lifetime. The “casus belli” concerns Giacinto Berruti, a member of the Mining Corps, the director of the Mining District in Turin, and one of Sella’s pupils. In a letter partially reported by Giordano (dated January 12th, 1881), Sella complains about Berruti seeing unfairly rejected his appointment as inspector. Giordano was astonished and shocked by this charge that would not go without consequences within the Corps of Mines and the Geological Service. In a few months’ time the dispute settled, as displayed in the correspondence, while Giordano was involved in new important events, such as the study of the Gotthard railway tunnel, the 2nd International Geological Congress in Bologna, the birth of the Italian Geological Society, and much more. On 26th of February 1884, Giordano writes his last letter to his friend, stuck at home because of poor health: the matter is the publication of the explanatory notes of the Geological map of Italy. Quintino Sella dies in Biella less than a month later (March 14th, 1884), at the age of 57. Felice Giordano survives him for eight years, with declining health and new bitterness at work, and dies July 16th 1892 in a tragic accident in Vallombrosa, near Florence.

Introduction: EGFR exon 20 insertion (ex20ins) mutations account for approximately 10% of EGFR mutations in lung adenocarcinoma. Patients with ex20ins mutation do not respond to standard EGFR tyrosine kinase inhibitor therapy. In this work, we analyzed the characteristics, treatment patterns, and outcomes in this subgroup of patients with NSCLC. Methods: The American Society of Clinical Oncology CancerLinQ Discovery data set was queried to identify patients with initial diagnosis of NSCLC between the years 1995 and 2018 and with EGFR ex20ins mutations. Data were extracted on patient demographics, tumor characteristics, treatments, and outcomes, and compared using chi-square and analysis of variance. Kaplan-Meier curves were generated to compare overall survival with log-rank tests. All analyses were performed using Python 3.6 (Python Software Foundation). Results: A total of 357 patients were eligible. Patient characteristics include a median age of 68 years comprising female sex of 54%, White race of 63%, and Black race of 9%. Approximately 62% of total patients had stage 4 disease, and 30% of all patients had brain metastasis. There were 54% of patients who were treated with chemotherapy and 15% with immune checkpoint inhibitors (ICIs). In patients with brain metastasis, 16% were treated with ICI, 18% with targeted therapy, and 59% with chemotherapy. The median survival of the entire group was 23.8 months. Among patients with stage 4 disease (n = 222): 51% were women, 64% were white, 37% had brain metastasis, 18% were treated with ICI, 14% had targeted therapy, and 60% were treated with chemotherapy. Stage 4 patients treated with targeted therapy had better survival compared with those who did not receive targeted therapy (20.6 versus 16.1 mo, p = 0.02). Univariate and multivariate analyses suggested favorable outcomes for patients treated with immunotherapy. Conclusions: EGFR ex20ins mutation represents a unique subset of NSCLC; it is associated with a higher propensity for brain metastases and a relatively modest overall survival. Novel treatment approaches are urgently needed to improve patient outcomes.

Abstract Background MET-driven acquired resistance is emerging with unanticipated frequency in patients relapsing upon molecular therapy treatments. However, the determination of MET amplification remains challenging using both standard and next-generation sequencing-based methodologies. Liquid biopsy is an effective, non-invasive approach to define cancer genomic profiles, track tumor evolution over time, monitor treatment response and detect molecular resistance in advance. Circular RNAs (circRNAs), a family of RNA molecules that originate from a process of back-splicing, are attracting growing interest as potential novel biomarkers for their stability in body fluids. Methods We identified a circRNA encoded by the MET gene (circMET) and exploited blood-derived cell-free RNA (cfRNA) and matched tumor tissues to identify, stratify and monitor advanced cancer patients molecularly characterized by high MET activity, generally associated with genomic amplification. Results Using publicly available bioinformatic tools, we discovered that the MET locus transcribes several circRNA molecules, but only one candidate, circMET, was particularly abundant. Deeper molecular analysis revealed that circMET levels positively correlated with MET expression and activity, especially in MET-amplified cells. We developed a circMET-detection strategy and, in parallel, we performed standard FISH and IHC analyses in the same specimens to assess whether circMET quantification could identify patients displaying high MET activity. Longitudinal monitoring of circMET levels in the plasma of selected patients revealed the early emergence of MET amplification as a mechanism of acquired resistance to molecular therapies. Conclusions We found that measurement of circMET levels allows identification and tracking of patients characterized by high MET activity. Circulating circMET (ccMET) detection and analysis could be a simple, cost-effective, non-invasive approach to better implement patient stratification based on MET expression, as well as to dynamically monitor over time both therapy response and clonal evolution during treatment.

Skeletal-related events (SREs) are complications of bone metastases and carry a significant patient and economic burden. Denosumab is a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor approved for SRE prevention in patients with multiple myeloma and patients with bone metastases from solid tumors. In phase 3 trials, denosumab showed superiority to the bisphosphonate zoledronate in reducing the risk of first on-study SRE by 17% (median time to first on-study SRE delayed by 8.2 months) and the risk of first and subsequent on-study SREs by 18% across multiple solid tumor types, including some patients with multiple myeloma. Denosumab also improved pain outcomes and reduced the need for strong opioids. Additionally, a phase 3 trial showed denosumab was noninferior to zoledronate in delaying time to first SRE in patients with newly diagnosed multiple myeloma. Denosumab has a convenient 120 mg every 4 weeks recommended dosing schedule with subcutaneous administration. Rare but serious toxicities associated with denosumab include osteonecrosis of the jaw, hypocalcemia, and atypical femoral fracture events, with multiple vertebral fractures reported following treatment discontinuation. After a decade of real-world clinical experience with denosumab, we are still learning about the optimal use and dosing for denosumab. Despite the emergence of novel and effective antitumor therapies, there remains a strong rationale for the clinical utility of antiresorptive therapy for SRE prevention. Ongoing studies aim to optimize clinical management of patients using denosumab for SRE prevention while maintaining safety and efficacy.

Lung cancer patients have been associated with an increased risk of COVID-19 infection, pulmonary complications, and worse survival outcomes compared to the general population. The world’s leading professional organizations provided new recommendations for the diagnosis, treatment, and follow-up of lung cancer patients during the pandemic as a guide for prioritizing cancer care issues. Telemedicine was preferred for non-urgent consultations, and screening programs were temporarily suspended, leading to possible diagnostic delays along with an estimated increase in cause-specific mortality. A vaccine campaign has recently emerged as the main weapon to fight the COVID-19 pandemic, inverting this negative trend. This work aims to provide a comprehensive overview of the epidemiology and immune-pathophysiology of SARS-CoV-2 infection in cancer patients, highlighting the most relevant changes in the clinical management of lung cancer patients during the pandemic.

Abstract Background Adenocarcinomas of the oral cavity are rare neoplasms, and only four cases of primary colonic adenocarcinoma of the tongue have ever been described in literature. Very few information about chemotherapy sensitiveness of this type of neoplasia is available, with only one regimen that showed some activity in a metastatic patient. Case presentation We describe the case of a patient bearing a metastatic colonic adenocarcinoma of the tongue submitted to a first-line chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid (FOLFOX regimen). After chemotherapy the patient obtained the complete disappearance of the primitive neoplasia located in the body of the tongue, and a tumor size reduction > 50% of liver and lung metastases. Conclusions This case demonstrated the activity of the combination of oxaliplatin and 5-fluorouracil in this very rare neoplasia. The FOLFOX regimen might be considered either in advanced and especially in the neoadjuvant setting, when the reduction of the primary tumor is highly needed.

Cancer cooperative groups have historically played a critical role in the advancement of non-small-cell lung cancer therapy. Representatives from cooperative groups worldwide convene at the International Lung Cancer Congress annually. The International Lung Cancer Congress had its 17th anniversary in the summer of 2016. The present review highlights the thoracic malignancy studies discussed by presenters. The included studies are merely a sample of the trials of thoracic malignancies ongoing globally.