Pulmonary blastoma: a comprehensive overview of a rare entity

Introduction: Pulmonary blastoma is a rare malignancy, accounting for less than 0.5% of primary lung tumors. It belongs to the group of pulmonary sarcomatoid carcinomas, and it is typically characterized by a biphasic pattern of an epithelial and a mesenchymal component. Only a few hundred cases have been reported worldwide. The aim of this study is to review and critically assess the literature regarding pulmonary blastoma.Material and methods: A narrative literature review of PubMed database from the inception of the database up to January 2021, limited to the English language, was conducted, using combinations of the following keywords: “pulmonary blastoma”, “biphasic pulmonary blastoma”, “sarcomatoid carcinoma”.Results: Pulmonary blastoma is composed of an epithelial and a mesenchymal malignant component. Regarding pathogenesis, the origin of the biphasic cell population remains elusive. Characteristic immunohistochemical stains are supportive of diagnosis.Clinically, the symptomatology is non-specific, while 40% of the cases are asymptomatic. It is diagnosed at a younger agecompared to other types of lung cancer, and it is often non-metastatic at diagnosis allowing for surgical treatment. Data on management and survival are scarce and mainly come from isolated cases. Advances on targeted therapy may provide novel treatment options. Given the rarity of the cases, multicenter collaboration is needed in order to establish therapeutic guidelines

Cyclin-Dependent Kinase 4/6 Inhibitors and Dermatologic Adverse Events: Results from the EADV Task Force "Dermatology for Cancer Patients"

Treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), has demonstrated significantly improved progression-free survival in patients with hormone receptor-positive, HER2-negative, advanced breast cancer, when used in combination with endocrine therapies. However, limited data exists on its cutaneous adverse events (AE). The aim of our retrospective study was to investigate the prevalence, types and management of cutaneous AE during CDK4/6i. 79 adult advanced breast cancer patients affected by 125 skin adverse events during treatment with CDK4/6i were recruited at eleven centers. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and ec-zematous lesions (24/79). We showed that skin reactions are usually mild in severity, and prompt management may limit the negative impact on patients, facilitating beneficial continuation of oncologic treatment

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist

The prognostic significance of soluble cell adhesion molecules in small-cell lung cancer: association with clinicopathological features

Background: Epithelial E-cadherin, intracellular cell adhesion molecule-1 (ICAM-1), vascularcell adhesion molecule-1 (VCAM-1) and endothelial E-selectin are transmembraneglycoproteins that actively participate in embryogenesis, maintenance of tissue architecture,immune responses and angiogenesis. Their expression has also proven to be of paramountsignificance in carcinogenesis, invasion and metastasis. This study assessed the prognostic roleof the afore-mentioned adhesion molecules serum levels before and during chemotherapyin patients with small-cell lung cancer. Patients & Methods: Blood samples from 50 patientsand 27 healthy controls were collected right before the initiation of chemotherapy, after 3cycles of chemotherapy, at the end of chemotherapy. Serum levels of ICAM-1 were measuredwith a commercial ELISA kit. Data were correlated with radiologic objective response andsurvival. Results: Statisticaly significant elevated values of all baseline soluble adhesionmolecules between patients and controls (p<0.001) were observed. Baseline ICAM-1 (HR:1.005, 95% CI 1.002-1.009, p=0.041) and E-selectin HR: 1.007, 95% CI 1.003-1.014,p=0.021) serum levels were found to be independent prognostic factors for a 12 monthsurvival. Performance status and disease stage were also independent prognostic factors.Patients who achieved an objective response during or after chemotherapy showed asignificant decrease (20% and 19%, respectively) in their soluble ICAM-1 levels comparedwith baseline levels (p=0.001 and p=0.012, respectively). Conclusions: The elevated serumlevels of all the examined cell adhesion molecules have proven their contribution in thedevelopment and behavior of small-cell lung cancer. Alongside performance status and diseasestage, baseline soluble ICAM-1 and E-selectin could be evaluated as additional prognosticfactors in patients with small-cell lung cancer. Also, a possible role for soluble ICAM-1 mayexist as a predictive marker for objective response during or after chemotherapy.Σκοπός: Η επιθηλιακή Ε-καντερίνη, το διακυτταρικό μόριο προσκόλλησης-1 (ΙCAM-1), τοαγγειακό μόριο προσκόλλησης-1 (VCAM-1) και η ενδοθηλιακή Ε-σελεκτίνη, είναιδιαμεμβρανικές γλυκοπρωτεΐνες, που συμμετέχουν στη διαδικασία της εμβρυογένεσης, στηδιατήρηση της δομής των ιστών, στη λειτουργία του ανοσοποιητικού συστήματος, στηναγγειογένεση. Η έκφρασή τους έχει αποδεικτεί ότι κατέχει σημαντικό ρόλο στηνκαρκινογένεση και στην εξέλιξη των νεοπλασιών. Η παρούσα προοπτική μελέτη εξέτασε τηνπρογνωστική σημασία των προαναφερόμενων μορίων προσκόλλησης στον μικροκυτταρικόκαρκίνο του πνεύμονα. Μέθοδοι: Συγκεντρώθηκαν δείγματα αίματος από 50νεοδιαγνωσθέντες ασθενείς με μικροκυτταρικό καρκίνο πνεύμονα καθώς και από 27 υγιείςμάρτυρες. Tα επιπεδα μετρήθηκαν με μέθοδο ELISA. Έγινε συσχέτιση των αποτελεσμάτωνμε τα χαρακτηριστικά των ασθενών, με την επιβίωση και με τις ανταποκρίσεις των ασθενώνστην χημειοθεραπεία. Αποτελέσματα: Διαπιστώθηκε στατιστικά σημαντική αύξηση τωνεπιπέδων όλων των εξετασθέντων μορίων των ασθενών κατά την διάγνωση συγκριτικά με τιςτιμές των μαρτύρων (p<0.001). Εκτός του σταδίου και του δείκτη λειτουργικής ικανότητας, ταεπίπεδα ICAM-1 (HR: 1.005, 95% CI 1.002-1.009, p=0.041) και Ε-σελεκτίνης (HR: 1.007,95% CI 1.003-1.014, p=0.021) ήταν ανεξάρτητοι προγνωστικοί παράγοντες επιβίωσης στους12 μήνες από την διάγνωση. Επιπλέον, οι ασθενείς που είχαν μείωση των επιπέδων τουICAM-1 κατά 20% στο μέσο και κατά 19% στο τέλος της χημειθεραπείας σε σχέση με τααρχικά τους επίπεδα, εμφάνισαν αντικειμενικές ανταποκρίσεις (p=0.001 και p=0.012αντίστοιχα). Συμπεράσματα: Με τα σημαντικά αυξημένα επίπεδα όλων των εξετασθέντωνδιαλυτών μορίων στην διάγνωση των ασθενών αποδεικνύεται η συμμετοχή τους στην εξέλιξητου μικροκυτταρικού καρκίνου του πνεύμονα. Το ICAM-1 και η Ε-σελεκτίνη θα μπορούσαννα χρησιμοποιηθούν ως πρόσθετοι προγνωστικοί παράγοντες. Το ICAM-1 ενδεχομένως ναέχει ρόλο προβλεπτικού δείκτη αντικειμενικής ανταπόκρισης

Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options

The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated the success story of targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy in patients with NSCLC with sensitizing EGFR mutations, as second-line therapy in patients who present the resistance-associated mutation T790M after treatment with previous EGFR-TKIs, and as adjuvant therapy for patients with early stage resected NSCLC, harboring EGFR mutations. Despite durable responses in patients with advanced NSCLC, resistance to osimertinib, similar to other targeted therapies, inevitably develops. Understanding the mechanisms of resistance, including both EGFR-dependent and -independent molecular pathways, as well as their therapeutic potential, represents an unmet need in thoracic oncology. Interestingly, differential resistance mechanisms develop when osimertinib is administered in a first-line versus second-line setting, indicating the importance of selection pressure and clonal evolution of tumor cells. Standard therapeutic approaches after progression to osimertinib include other targeted therapies, when a targetable genetic alteration is detected, and cytotoxic chemotherapy with or without antiangiogenic and immunotherapeutic agents. Deciphering the when and how to use immunotherapeutic agents in EGFR-positive NSCLC is a current challenge in clinical lung cancer research. Emerging treatment options after progression to osimertinib involve combinations of different therapeutic approaches and novel EGFR-TKI inhibitors. Research should also be focused on the standardization of liquid biopsies in order to facilitate the monitoring of molecular alterations after progression to osimertinib

Profile of capecitabine/temozolomide combination in the treatment of well-differentiated neuroendocrine tumors

Elias A Kotteas,1 Konstantinos N Syrigos,1,2 Muhammad Wasif Saif3 1Oncology Unit, Sotiria General Hospital, University of Athens, Athens, Greece; 2Thoracic Oncology Program, Yale School of Medicine, New Haven, CT, USA; 3Section of GI and Experimental Therapeutics, Tufts University School of Medicine, Boston,&nbsp;MA, USA Abstract: Neuroendocrine tumors are a rare and heterogeneous group of tumors with a variety of primary origins and variable aggressiveness. Platinum-based chemotherapy has been the cornerstone of treatment for the poorly differentiated tumors. However, well-differentiated neuroendocrine tumors are quite chemoresistant and therapy options are limited. Octreotide analogs and tyrosine kinase inhibitors are widely acceptable treatments due to substantial efficacy and tolerable toxicity. On the contrary, monotherapy or combinations of the only approved cytotoxic agent streptozocin with other drugs have been almost abandoned because of excessive toxic events. In recent years, the combination of capecitabine and temozolomide has emerged as the most promising and efficacious treatment. The oral route of administration and the substantial improvement in the outcomes with manageable toxicity are the major advantages. We reviewed the current literature and presented the profile of the capecitabine/temozolomide combination in the management of well-differentiated neuroendocrine tumors. Keywords: capecitabine, neuroendocrine tumors, octreotide analogs, streptozocin, temozolomide, toxicit

Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options

The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated the success story of targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy in patients with NSCLC with sensitizing EGFR mutations, as second-line therapy in patients who present the resistance-associated mutation T790M after treatment with previous EGFR-TKIs, and as adjuvant therapy for patients with early stage resected NSCLC, harboring EGFR mutations. Despite durable responses in patients with advanced NSCLC, resistance to osimertinib, similar to other targeted therapies, inevitably develops. Understanding the mechanisms of resistance, including both EGFR-dependent and -independent molecular pathways, as well as their therapeutic potential, represents an unmet need in thoracic oncology. Interestingly, differential resistance mechanisms develop when osimertinib is administered in a first-line versus second-line setting, indicating the importance of selection pressure and clonal evolution of tumor cells. Standard therapeutic approaches after progression to osimertinib include other targeted therapies, when a targetable genetic alteration is detected, and cytotoxic chemotherapy with or without antiangiogenic and immunotherapeutic agents. Deciphering the when and how to use immunotherapeutic agents in EGFR-positive NSCLC is a current challenge in clinical lung cancer research. Emerging treatment options after progression to osimertinib involve combinations of different therapeutic approaches and novel EGFR-TKI inhibitors. Research should also be focused on the standardization of liquid biopsies in order to facilitate the monitoring of molecular alterations after progression to osimertinib

Treating patients with ALK-rearranged non-small-cell lung cancer: mechanisms of resistance and strategies to overcome it

Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases. Ceritinib and alectinib are the only approved drugs of this group. Many ongoing trials try to define the most appropriate agent for the treatment of ALK-positive lung cancer depending on the responsible mechanism. This review focuses on the current data regarding the potential mechanisms of resistance to ALK inhibitors and the strategies to overcome it