The Role of ctDNA in the Management of Non-Small-Cell Lung Cancer in the AI and NGS Era.

Liquid biopsy (LB) involves the analysis of circulating tumour-derived DNA (ctDNA), providing a minimally invasive method for gathering both quantitative and qualitative information. Genomic analysis of ctDNA through next-generation sequencing (NGS) enables comprehensive genetic profiling of tumours, including non-driver alterations that offer prognostic insights. LB can be applied in both early-stage disease settings, for the diagnosis and monitoring of minimal residual disease (MRD), and advanced disease settings, for monitoring treatment response and understanding the mechanisms behind disease progression and tumour heterogeneity.

Alectinib for the treatment of papillary thyroid carcinoma harbouring STRN - ALK fusion.

Background: Anaplastic Lymphoma Kinase (ALK) rearrangement is a rare alteration in differentiated thyroid carcinomas (DTCs). Due to its low prevalence, a few evidence are available about the use of ALK inhibitors in advanced DTCs.

Methods: We report the case of a striatin (STRN) - ALK translocated advanced thyroid carcinoma.

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.

Proton and photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and adjuvant immune therapy.

Background And Purpose: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment.

Perioperative Treatment Strategies in EGFR-Mutant Early-Stage NSCLC: Current Evidence and Future Challenges.

Treatment with 3 years of adjuvant osimertinib is considered a new standard in patients with completely resected stage I to IIIA NSCLC harboring a common sensitizing EGFR mutation. This therapeutic approach significantly prolonged the disease-free survival and the overall survival versus placebo and revealed a significant role in preventing the occurrence of brain metastases. However, many unanswered questions remain, including the optimal duration of this therapy, whether all patients benefit from adjuvant osimertinib, and the role of adjuvant chemotherapy in this population.

Unveiling the Potential of Venn Diagrams as a Helpful Tool for Clinical Reasoning: An Illustrative Case-based Discussion.

Venn diagrams graphically represent a cognitive approach that can assist in highlighting information shared by different data sets while eliminating nonoverlapping conditions. When applied to clinical reasoning, such an approach helps physicians visually focus on data pertaining to differential diagnoses. We present and discuss a 3-step reasoning pathway derived from a real-life case in which we used Venn diagrams to diagnose drug-related pneumonitis in a 67-year-old man with advanced bladder cancer and nodular lung findings at chest CT.

The Association of Gross Tumor Volume and Its Radiomics Features with Brain Metastases Development in Patients with Radically Treated Stage III Non-Small Cell Lung Cancer.

Purpose: To identify clinical risk factors, including gross tumor volume (GTV) and radiomics features, for developing brain metastases (BM) in patients with radically treated stage III non-small cell lung cancer (NSCLC).

Methods: Clinical data and planning CT scans for thoracic radiotherapy were retrieved from patients with radically treated stage III NSCLC. Radiomics features were extracted from the GTV, primary lung tumor (GTVp), and involved lymph nodes (GTVn), separately.

Adjuvant durvalumab after concurrent chemoradiotherapy for patients with unresectable stage III NSCLC harbouring uncommon genomic alterations.

Adjuvant durvalumab is the standard of care for patients with stage III unresectable non-small cell lung cancer (NSCLC), without progression after concurrent chemo-radiation (CCRT). Patients with stage III NSCLC harbouring epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangements do not seem to benefit from durvalumab. Data are lacking about patients harbouring other driver genomic alterations (dGA).

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.

T790M testing through repeated liquid biopsy over time: a real-world multicentric retrospective experience.

Background: About 15% of non-small cell lung cancers (NSCLCs) harbor epidermal growth factor receptor () mutations. Upfront treatment with first and second generation EGFR tyrosine kinase inhibitors (1-2gen TKIs) is superior to chemotherapy. The most frequent resistance mechanism to 1-2gen TKIs is T790M mutation, which is targeted by osimertinib.

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.

Physical exercise at the crossroad between muscle wasting and the immune system: implications for lung cancer cachexia.

Cachexia is a syndrome characterized by involuntary weight loss and wasting of skeletal muscle mass. It is associated with worse overall survival and quality of life. The cancer-induced systemic inflammation and the consequent host derived catabolic stimuli, trigger cachexia by inhibiting muscle protein synthesis and enhancing muscle catabolism.

Synaptophysin expression in mutated advanced colorectal cancers identifies a new subgroup of tumours with worse prognosis.

Background: Neuroendocrine differentiation has been extensively associated with worse prognosis and to mechanisms of therapy resistance in several epithelial cancers. A high prevalence of neuroendocrine differentiation was recently described in mutated (BRAFmt) metastatic colorectal cancers (mCRCs) but no data are available about its prognostic impact in this setting.

Methods: We assessed synaptophysin immunohistochemical expression in a multi-institutional series of 159 BRAFmt mCRCs with matched clinical and pathological information.

A Multi-Center, Real-Life Experience on Liquid Biopsy Practice for EGFR Testing in Non-Small Cell Lung Cancer (NSCLC) Patients.

Background: circulating tumor DNA (ctDNA) is a source of tumor genetic material for EGFR testing in NSCLC. Real-word data about liquid biopsy (LB) clinical practice are lacking. The aim of the study was to describe the LB practice for EGFR detection in North Eastern Italy.

Determinants of choice in offering drug holidays during first-line therapy for metastatic colorectal cancer.

'Drug holidays' (DH) for metastatic colorectal cancer (mCRC) were introduced to preserve quality of life. We studied factors associated to a DH offer in first line. We retrospectively analyzed 754 consecutive patients treated with chemotherapy for mCRC in two Italian institutions between 2005 and 2017.

Seven Shades of Black Thoughts: COVID-19 and Its Psychological Consequences on Cancer Patients.

An outbreak of novel coronavirus disease (COVID-19) that started in China at the end of 2019 has rapidly spread all over the world. COVID-19 is plaguing people not only physically but also psychologically, and cancer patients are particularly exposed to this emotional threat. Herein, we describe the psychological threats posed by COVID-19 to cancer patients.

Platinum-Based Chemotherapy in Older Patients with Non-Small Cell Lung Cancer: What to Expect in the Real World.

Background: The role of platinum-based chemotherapy (PBC) for the treatment of older patients with non-small cell lung cancer (NSCLC) is still a matter of debate, despite the advent of immunotherapy.

Objective: The aim of the study was to identify factors associated with first-line PBC prescription and, secondly, to evaluate the impact of first-line PBC on survival, treatment intensity, risk of hospitalization, and subsequent treatments.

Patients And Methods: We reviewed a consecutive series of 474 older patients (age ≥ 70 years) diagnosed with stage IIIB-IV NSCLC at the Department of Oncology, University Hospital of Udine, Italy from January 2009 to March 2017.

The MIMIC Study: Prognostic Role and Cutoff Definition of Monocyte-to-Lymphocyte Ratio and Lactate Dehydrogenase Levels in Metastatic Colorectal Cancer.

Background: Monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels are circulating biomarkers that provide information about tumor-related inflammation and immune suppression. This study aimed to evaluate the prognostic role of MLR and LDH in metastatic colorectal cancer (mCRC).

Material And Methods: This multicentric study analyzed a consecutive cohort of 528 patients with mCRC treated in 2009-2017.

Emerging therapies in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare cancer of the pleural surfaces frequently related to asbestos exposure. It is characterized by a poor prognosis even for patients treated with trimodality therapy, including surgery, chemotherapy and radiotherapy. Moreover, the majority of patients are not candidates for surgery due to disease advanced stage or medical comorbidities.

CK7 and consensus molecular subtypes as major prognosticators in BRAF mutated metastatic colorectal cancer.

Background: BRAF mutated metastatic colorectal cancer (mCRC) is a subtype (10%) with overall poor prognosis, but the clinical experience suggests a great heterogeneity in survival. It is still unexplored the real distribution of traditional and innovative biomarkers among BRAF mutated mCRC and which is their role in the improvement of clinical prediction of survival outcomes.

Methods: Data and tissue specimens from 155 BRAF mutated mCRC patients treated at eight Italian Units of Oncology were collected.

Lack of Benefit From Anti-EGFR Treatment in RAS and BRAF Wild-type Metastatic Colorectal Cancer With Mucinous Histology or Mucinous Component.

Background: Adenocarcinoma with mucinous histology or mucinous component are histologic subtypes of metastatic colorectal cancers (mCRCs) with limited benefit from cytotoxic agents. Their sensitivity to anti-epithelial growth factor receptors (EGFRs) is not clear.

Patients And Methods: The activity and efficacy of anti-EGFRs was retrospectively evaluated among patients with RAS and BRAF wild-type mCRC with or without mucinous histology or mucinous component.