Targeting EGFR T790M mutation in NSCLC: From biology to evaluation and treatment.

The identification of EGFR mutations and their respectively tyrosine kinase inhibitors (TKIs), changed dramatically treatment and survival of patients with EGFR-positive lung cancer. Nowadays, different EGFR TKIs as afatinib, erlotinib and gefitinib are approved worldwide for the treatment of NSCLC harbouring EGFR mutations, in particular exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. In first-line setting, when comparing with platinum-based chemotherapy, these target drugs improves progression-free survival, response rate and quality of life. Unfortunately, the development of different mechanism of resistance, limits the long term efficacy of these agents. The most clear mechanism of resistance is the development of EGFR Thr790Met mutation. Against this new target, different third-generation EGFR-mutant-selective TKIs, such as osimertinib, rociletinib and olmutinib, showed a great activity. In this review, we summarize the scientific evidences about biology, evaluation and treatment on NSCLC with EGFR T790M mutation.

CT Radiogenomic Characterization of EGFR, K-RAS, and ALK Mutations in Non-Small Cell Lung Cancer.

OBJECTIVES: To assess the association between CT features and EGFR, ALK, KRAS mutations in non-small cell lung cancer. METHODS: Patients undergoing chest CT and testing for the above gene mutations were included. Qualitative evaluation of CTs included: lobe; lesion diameter; shape; margins; ground-glass opacity; density; cavitation; air bronchogram; pleural thickening; intratumoral necrosis; nodules in tumour lobe; nodules in non-tumour lobes; pleural retraction; location; calcifications; emphysema; fibrosis; pleural contact; pleural effusion. Statistical analysis was performed to assess association of features with each gene mutation. ROC curves for gene mutations were drawn; the corresponding area under the curve was calculated. P-values <0.05 were considered significant. RESULTS: Of 285 patients, 60/280 (21.43 %) were positive for EGFR mutation; 31/270 (11.48 %) for ALK rearrangement; 64/240 (26.67 %) for KRAS mutation. EGFR mutation was associated with air bronchogram, pleural retraction, females, non-smokers, small lesion size, and absence of fibrosis. ALK rearrangements were associated with age and pleural effusion. KRAS mutation was associated with round shape, nodules in non-tumour lobes, and smoking. CONCLUSIONS: This study disclosed associations between CT features and alterations of EGFR (air bronchogram, pleural retraction, small lesion size, absence of fibrosis), ALK (pleural effusion) and KRAS (round lesion shape, nodules in non-tumour lobes). KEY POINTS: Air bronchogram, pleural retraction, small size relate to EGFR mutation in NSCLC. Pleural effusion and younger age relate to ALK mutation. Round lesion shape, nodules in non-tumour lobes relate to KRAS mutation.

Molecular features and clinical outcome of lung malignancies in very young people.

INTRODUCTION: We describe the clinical features, outcome and incidence of druggable targets of lung cancers in patients ≤ 40 years old. MATERIALS & METHODS: Young patients were compared with two other groups (41-64 and ≥ 65 years). Neuroendocrine tumors, adenocarcinoma and non-adenocarcinoma/unspecified non-small-cell lung cancer were analyzed separately. Molecular characteristics of adenocarcinoma were evaluated in a subset of young patients. RESULTS: Of 2847 patients with lung cancer, 100 were ≤ 40 years old. The young group contained more women, never-smokers and patients presenting with advanced disease. The commonest tumor in young patients was adenocarcinoma. In total, 19 of 34 young patients with adenocarcinoma had tumors with specific molecular alterations. CONCLUSION: Lung cancers in young patients have distinctive features but outcomes similar to those in older patients.

Phase ib of sorafenib in combination with everolimus in patients with advanced solid tumors, selected on the basis of molecular targets.

BACKGROUND: Molecular alterations of the PI3K and Ras pathways often occur in human cancer. In this trial, the pharmacokinetics, toxicity, and activity of two drugs inhibiting these pathways-everolimus and sorafenib-were investigated. METHODS: Thirteen patients with progressing solid tumors were treated with everolimus and sorafenib, according to a 3+3 scheme. Patients were selected on the basis of immunohistochemical expression of tumor molecular targets, including phospho-AKT, -p70S6K, and -ERK1/2. RESULTS: The daily recommended dose identified was 2.5 mg of everolimus and 600 mg of sorafenib. Dose-limiting toxicities included grade 3 asthenia and hand-foot skin reaction. No grade 4 adverse events were observed. The most frequent grade 3 toxicities were hypophosphatemia (30.8%), alanine aminotransferase level increase, asthenia, and anorexia (14%). No pharmacokinetic interactions were identified between everolimus and sorafenib. Of 12 evaluable patients, we observed 2 partial responses, with greater than 10% shrinkage in an additional 5 patients. Objective responses were observed in one patient with a thymoma and in one patient with a lung adenocarcinoma. Tumor shrinkage that did not qualify as a partial response was seen in an abdominal leiomyosarcoma and in adenoid cystic carcinomas. CONCLUSION: The combination of everolimus and sorafenib is safe. The tumor activity observed in different tumor types could be the result of the combined action of these drugs as well as the molecular selection of the treated population. Further research is warranted to better investigate drugs simultaneously blocking the PI3K and the Ras pathways and to refine patient selection.

Post-Progression Analysis of EGFR-Mutant NSCLC Following Osimertinib Therapy in Real-World Settings.

BACKGROUND: Platinum-based chemotherapy is the current standard treatment option in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this setting. METHODS: Patients with EGFR-mutant NSCLC who were candidates to receive osimertinib in the metastatic setting at our Center from 2015 to 2022 were retrospectively evaluated to identify patients who received standard platinum-based chemotherapy post-osimertinib. Data were collected on treatment outcomes, with a focus on brain metastases and progression patterns. RESULTS: A total of 220 patients received indication for osimertinib in the study period; n = 176 had adequate follow-up data. Overall, n = 117 patients experienced disease progression on osimertinib. The median time to osimertinib progressive disease (PD) was 15 months (95% confidence interval CI 13-18). Of them, 51 patients (45%) had no access to further treatments. Of the remaining patients, n = 8 received experimental treatments, and n = 55 received standard platinum-based chemotherapy and were considered for this study. Median duration of chemotherapy was 3 months (95% CI 2-5); the best responses among 53 evaluable patients were observed as follows: 15% partial response/complete response (PR/CR), 40% stable disease (SD), 45% PD. Median progression-free survival (PFS) and overall survival (OS) were 3 (95% CI 2-5) and 10 (95% CI 6-15) months, respectively. All patients had baseline and follow-up brain radiologic assessments, and n = 23 had brain metastases at the start of chemotherapy. With a median follow-up of 13 months, intracranial PD occurred in 47% patients, being the first site of PD in 59% of cases. The median time for intracranial (IC) PD was 2 months (95% CI 2-7). IC PD occurred as oligometastatic in 29%, whereas in 71% of cases, it was associated with systemic PD. CONCLUSIONS: Access to subsequent treatments and CNS progression are confirmed unmet needs in EGFR-mutant NSCLC patients. Clinical and CNS-specific outcomes in patients receiving standard chemotherapy after the failure of osimertinib are dismal. Novel upfront treatment options with demonstrated prolonged PFS and better CNS outcomes may help address this important issue.

Alectinib vs. Lorlatinib in the Front-Line Setting for ALK-Rearranged Non-Small-Cell Lung Cancer (NSCLC): A Deep Dive into the Main Differences across ALEX and CROWN Phase 3 Trials.

Various next-generation ALK TKIs are available as first-line options for ALK-positive NSCLC, with alectinib and lorlatinib being commonly preferred. However, no direct comparison between them has been conducted, making it impossible to pick a winner. We performed an analytic, 'non-comparative' assessment of the two phase 3 pivotal clinical trials showing superiority of alectinib (ALEX) and lorlatinib (CROWN) in comparison to crizotinib. Overall, the two studies were very similar in the study design and patient characteristics, with the exception of the selection and evaluation of brain metastases. PFS hazard ratios numerically favored lorlatinib, both according to the investigator and to BICR. Notably, the 3-year PFS rate was numerically higher with lorlatinib (64%) than with alectinib (46.4%). Despite similar response rates and overall intracranial response, the rate of complete intracranial response was higher with lorlatinib, with a cumulative incidence risk of CNS disease progression at 12 months of 9.4% with alectinib and 2.8% with lorlatinib. The peculiar toxicities of lorlatinib were related to lipidic profile alterations, peripheral oedema and cognitive effects, with no impact on cardiovascular risk nor impairment in quality of life versus crizotinib. Furthermore, the rate of permanent treatment discontinuation due to adverse events was numerically higher with alectinib (26%) than with lorlatinib (7%). In conclusion, despite the immature OS data for both drugs, the efficacy of lorlatinib appears higher than alectinib while maintaining a manageable toxicity profile.

The Evolving Scenario of ES-SCLC Management: From Biology to New Cancer Therapeutics.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma accounting for 15% of lung cancers with dismal survival outcomes. Minimal changes in therapy and prognosis have occurred in SCLC for the past four decades. Recent progress in the treatment of extensive-stage disease (ES-SCLC) has been marked by incorporating immune checkpoint inhibitors (ICIs) into platinum-based chemotherapy, leading to modest improvements. Moreover, few second-line-and-beyond treatment options are currently available. The main limitation for the molecular study of SCLC has been the scarcity of samples, because only very early diseases are treated with surgery and biopsies are not performed when the disease progresses. Despite all these difficulties, in recent years we have come to understand that SCLC is not a homogeneous disease. At the molecular level, in addition to the universal loss of retinoblastoma (RB) and TP53 genes, a recent large molecular study has identified other mutations that could serve as targets for therapy development or patient selection. In recent years, there has also been the identification of new genetic subtypes which have shown us how intertumor heterogeneity exists. Moreover, SCLC can also develop intratumoral heterogeneity linked mainly to the concept of cellular plasticity, mostly due to the development of resistance to therapies. The aim of this review is to quickly present the current standard of care of ES-SCLC, to focus on the molecular landscapes and subtypes of SCLC, subsequently present the most promising therapeutic strategies under investigation, and finally recap the future directions of ongoing clinical trials for this aggressive disease which still remains a challenge.

Co-Occurring Driver Genomic Alterations in Advanced Non-Small-Cell Lung Cancer (NSCLC): A Retrospective Analysis.

Background: Actionable driver mutations account for 40-50% of NSCLC cases, and their identification clearly affects treatment choices and outcomes. Conversely, non-actionable mutations are genetic alterations that do not currently have established treatment implications. Among co-occurring alterations, the identification of concurrent actionable genomic alterations is a rare event, potentially impacting prognosis and treatment outcomes. Methods: We retrospectively evaluated the prevalence and patterns of concurrent driver genomic alterations in a large series of NSCLCs to investigate their association with clinicopathological characteristics, to assess the prognosis of patients whose tumor harbors concurrent alterations in the genes of interest and to explore their potential therapeutic implications. Results: Co-occurring driver alterations were identified in 26 out of 1520 patients with at least one gene alteration (1.7%). Within these cases, the incidence of concurrent actionable gene alterations was 39% (0.7% of the overall cohort). Among compound actionable gene mutations, EGFR was the most frequently involved gene (70%). The most frequent association was EGFR mutations with ROS1 rearrangement. Front-line targeted treatments were the preferred approach in patients with compound actionable mutations, with dismal median PFS observed (6 months). Conclusions: Advances in genomic profiling technologies are facilitating the identification of concurrent mutations. In patients with concurrent actionable gene alterations, integrated molecular and clinical data should be used to guide treatment decisions, always considering rebiopsy at the moment of disease progression.

Immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: A systematic review.

BACKGROUND: Since their first introduction in clinical practice, immune checkpoint inhibitors showed limited benefit in patients with NSCLC harboring EGFR mutations. With the rationale of increasing immune activation, combinatorial ICI strategies have been evaluated also in this subgroup of patients. METHODS: We performed a systematic review on efficacy of ICI-based strategies in EGFR-mutant NSCLC according to most updated evidence. RESULTS: Overall, ICI monotherapy and ICI plus chemotherapy confirm to be ineffective in EGFR-mutant NSCLC, whereas the combination of ICI with antiangiogenic and chemotherapy showed promising results. Limited data are available with alternative ICI combination strategies, driven by strong biological rationale of modulating the tumor immune microenvironment. CONCLUSIONS: To date, the available evidence do not support the use of ICI in patients with NSCLC harboring EGFR mutations. Clinical trials are ongoing to define which is the best timing and exploring novel combinations with ICI in this specific disease.

New Generations of Tyrosine Kinase Inhibitors in Treating NSCLC with Oncogene Addiction: Strengths and Limitations.

Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring most driver gene alterations. Starting from the first generation, research rapidly moved to the development of newer, more selective generations of TKIs, obtaining improved results in terms of disease control and survival. However, the use of novel generations of TKIs is not without limitations. We reviewed the main results obtained, as well as the ongoing clinical trials with TKIs in oncogene-addicted NSCLC, together with the biology underlying their potential strengths and limitations. Across driver gene alterations, novel generations of TKIs allowed delayed resistance, prolonged survival, and improved brain penetration compared to previous generations, although with different toxicity profiles, that generally moved their use from further lines to the front-line treatment. However, the anticipated positioning of novel generation TKIs leads to abolishing the possibility of TKI treatment sequencing and any role of previous generations. In addition, under the selective pressure of such more potent drugs, resistant clones emerge harboring more complex and hard-to-target resistance mechanisms. Deeper knowledge of tumor biology and drug properties will help identify new strategies, including combinatorial treatments, to continue improving results in patients with oncogene-addicted NSCLC.

MET in Non-Small-Cell Lung Cancer (NSCLC): Cross 'a Long and Winding Road' Looking for a Target.

Non-Small-Cell Lung Cancer (NSCLC) can harbour different MET alterations, such as MET overexpression (MET OE), MET gene amplification (MET AMP), or MET gene mutations. Retrospective studies of surgical series of patients with MET-dysregulated NSCLC have shown worse clinical outcomes irrespective of the type of specific MET gene alteration. On the other hand, earlier attempts failed to identify the 'druggable' molecular gene driver until the discovery of MET exon 14 skipping mutations (METex14). METex14 are rare and amount to around 3% of all NSCLCs. Patients with METex14 NSCLC attain modest results when they are treated with immune checkpoint inhibitors (ICIs). New selective MET inhibitors (MET-Is) showed a long-lasting clinical benefit in patients with METex14 NSCLC and modest activity in patients with MET AMP NSCLC. Ongoing clinical trials are investigating new small molecule tyrosine kinase inhibitors, bispecific antibodies, or antibodies drug conjugate (ADCs). This review focuses on the prognostic role of MET, the summary of pivotal clinical trials of selective MET-Is with a focus on resistance mechanisms. The last section is addressed to future developments and challenges.

Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?

ALK translocation amounts to around 3-7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progression-free survival and brain metastases management. Unfortunately, most patients develop acquired resistance to ALK-Is that is mediated by on- and off-target mechanisms. Translational and clinical research are continuing to develop new drugs and/or combinations in order to raise the bar and further improve the results attained up to now. This review summarizes first-line randomized clinical trials of several ALK-Is and the management of brain metastases with a focus on ALK-I resistance mechanisms. The last section addresses future developments and challenges.

Association between Contrast-Enhanced Computed Tomography Radiomic Features, Genomic Alterations and Prognosis in Advanced Lung Adenocarcinoma Patients.

Non-invasive methods to assess mutational status, as well as novel prognostic biomarkers, are warranted to foster therapy personalization of patients with advanced non-small cell lung cancer (NSCLC). This study investigated the association of contrast-enhanced Computed Tomography (CT) radiomic features of lung adenocarcinoma lesions, alone or integrated with clinical parameters, with tumor mutational status (EGFR, KRAS, ALK alterations) and Overall Survival (OS). In total, 261 retrospective and 48 prospective patients were enrolled. A Radiomic Score (RS) was created with LASSO-Logistic regression models to predict mutational status. Radiomic, clinical and clinical-radiomic models were trained on retrospective data and tested (Area Under the Curve, AUC) on prospective data. OS prediction models were trained and tested on retrospective data with internal cross-validation (C-index). RS significantly predicted each alteration at training (radiomic and clinical-radiomic AUC 0.95-0.98); validation performance was good for EGFR (AUC 0.86), moderate for KRAS and ALK (AUC 0.61-0.65). RS was also associated with OS at univariate and multivariable analysis, in the latter with stage and type of treatment. The validation C-index was 0.63, 0.79, and 0.80 for clinical, radiomic, and clinical-radiomic models. The study supports the potential role of CT radiomics for non-invasive identification of gene alterations and prognosis prediction in patients with advanced lung adenocarcinoma, to be confirmed with independent studies.

The new era of immune checkpoint inhibition and target therapy in early-stage non-small cell lung cancer. A review of the literature.

Surgery is the best option for patients with early stage non-small cell lung cancer (NSCLC). However, the rate of local and metastatic recurrences following surgery alone is high, especially in NSCLC patients with N2 lymph node involvement. A recent American study showed that 60% of lung cancers are diagnosed in an advanced stage, and less than 20% are diagnosed in an early, resectable stage. The same study reported the 5 year survival of patients with stage IV NSCLC was 6% compared to 50% in patients with resectable NSCLC depending by stage. The addition of adjuvant or neoadjuvant chemotherapy only improves 5 year survival by 5%-10%. Recently, immunotherapy with or without chemotherapy and novel targeted therapies have yielded excellent results, in terms of both progression-free survival and overall survival, in advanced NSCLC. Published studies have shown a benefit in using immunotherapy and targeted therapy in both the adjuvant and neoadjuvant settings with many further studies still ongoing. Here we review the published data on immunotherapy and targeted therapy in the adjuvant and neoadjuvant settings in patients with operable NSCLC.

Comparison of real-world data (RWD) analysis on efficacy and post-progression outcomes with pembrolizumab plus chemo vs chemo alone in metastatic non-squamous non-small cell lung cancer with PD-L1 < 50.

Background: Following the introduction of immunotherapy (IO) in the first-line (1L) treatment in patients with non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK mutations, increasing real-world data depict how difficult it is to replicate data from clinical trials to clinical practice, with high rates of early treatment failure. In the context of chemo-IO, our study aims to compare platinum-pemetrexed-pembrolizumab combination to platinum-doublet alone in patients with low PD-L1 (<50%). Methods: We retrospectively collected medical records from patients with stage IV non-squamous NSCLC with PD-L1<50%, consecutively treated at our Centre from 2016 to 2021. Patients were grouped according to 1L treatment received: chemo-IO (group A) or platinum-doublet (group B). Survival outcomes were analyzed and compared among the two groups. Results: Overall, 105 patients were included: 49 in group A and 56 in group B. At data cut-off, median follow-up was 12.4 and 34.8 months, with 32/49 and 52/56 events for progression-free survival (PFS) and 21/49 and 29/56 events for overall survival (OS), respectively. No difference in PFS was observed between group B and group A (6.6 versus 8 months, HR 1.12, 95%CI 0.57-1.40). Patients receiving 1L platinum-doublet had significantly longer OS compared to those receiving chemo-IO (median OS 23.8 vs 14.9 months, HR 0.47, 95% CI 1.15- 3.98, p=0.01). 12 month-OS was 58% (95% CI 44-76%) in group A and 78% (95% CI 68-91%) in group B (p=0.040). Subgroup analysis identified KRAS G12C mutation as potentially affecting PFS in patients receiving chemo-IO (HR 0.29, 95% CI 0-10-0.91). The OS benefit of platinum-doublet was consistent across subgroups, with particular benefit in female sex, liver or pleural metastases, PD-L1 negative. Overall, only 46.9% of patients with progression received subsequent treatment in group A (15/32), compared to 86.5% in group B (45/52, all receiving 2L IO), with no difference in PFS to 2L (group A 3.7months, group B 4.1months, p=0.3). Conclusions: Despite small study population and differential follow-up, our study demonstrates that sequential use of 1L platinum-doublet and 2L IO is not inferior to 1L chemo-IO in non-squamous NSCLC with PD-L1<50%. In addition, we identified subgroups who might benefit differentially from the two approaches.

Association between changes in thioredoxin reductase and other peripheral blood biomarkers with response to PD-1 inhibitor-based combination immunotherapy in non-small cell lung cancer: a retrospective study.

Background: Immunotherapy deeply changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC) in the past years. However, the objective response rate (ORR) after immunotherapy is about 20-30% of NSCLC patients. Therefore, identification of predictive biomarkers is crucial for selecting patients with NSCLC who would most benefit from programmed cell death receptor protein 1 (PD-1) inhibitor-based immunotherapy. Methods: We retrospectively collected medical records and thioredoxin reductase (TrxR) data from 90 patients with a NSCLC who received PD-1 inhibitor-based combination therapy. Serum biomarkers were also measured at 6- and 12-week post-treatment and compared with their baseline values. Associations between changes in serum biomarkers, clinical characteristics and treatment efficacy were evaluated using univariate tests. The patients who were still alive were followed up remotely by phone or email to assess survival. The association between serum biomarkers and TrxR with overall survival (OS) and progression-free survival (PFS) were assessed by univariate and multivariate Cox proportional hazard regression. Nomogram prediction models were constructed using factors associated with PFS and OS, respectively. Results: The median follow-up time among the 90 patients was 19.7 (range, 13.6 to 25.8) months. Median PFS and OS were 13.6 [95% confidence interval (CI): 13.5 to 13.7] and 19.7 (95% CI: 13.6 to 25.8) months, respectively. Patients with decreased carcinoembryonic antigen (CEA), albumin (Alb), and TrxR values at 6- and 12-week post-treatment compared to baseline had statistically significantly improved disease remission rates (P<0.05). Patients with decreased white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR) at week 6, and decreased Alb, CEA, and lymphocyte-to-monocyte ratio (LMR) at week 12 had statistically significantly increased ORRs (P<0.05). According to the univariate and multivariate Cox regression analyses, we included adenocarcinoma, Eastern Cooperative Oncology Group performance status (ECOG PS), and CEA change at week 6 post-treatment as predictors for PFS, and adenocarcinoma, change in absolute lymphocyte count (ALC), and TrxR at week 6 as predictors for OS in the nomogram models. Each nomogram was also validated internally using a bootstrap method with 1,000 resamples. Conclusions: Change in TrxR at 6 weeks post-treatment in combination with other clinical and hematological biomarkers could be used as a predictor for treatment outcome and prognosis in NSCLC patients after PD-1 inhibitor-based combination immunotherapy.

"Waiting and the waiting room: how do you experience them?" emotional implications and suggestions from patients with cancer.

Waiting can increase discomfort. The goal of this study was to identify moods and fears of cancer patients while in a waiting room and to capture their concrete suggestions for an anthropocentric transformation of waiting itself. A 15-item questionnaire was given to 355 patients who came to our Out-patient Oncology Clinic. Eighty-three percent of patients felt that waiting has an emotional cost, 35% were upset by talking about their condition with others while waiting, and 26% suffered a major emotional impact seeing other sick people and witnessing their clinical decline. Eighty-nine percent of patients suggested that alternative activities, such as meetings with professionals, doctors, and psychologists, be organized during the waiting period; 65% suggested fun activities (music therapy, drawing courses, library, TV). Most patients asked to have the freedom to leave the waiting room. This option, feasibly by means of IMs/"beepers," would limit their sense of having a lack of freedom or being robbed of their time. This study highlighted the complexity and heterogeneity of emotional implications that waiting causes in patients with cancer and collected many patients' suggestions about how to create a constructive, free, and personalized waiting period, overcoming the boredom, distress, and psychological suffering it causes.

Interstitial pneumonitis in the COVID-19 era: a difficult differential diagnosis in patients with lung cancer.

In this coronavirus 2019 (COVID-19) era, when pneumonitis occurs in patients with lung cancer receiving immune checkpoint inhibitors (ICIs), a major challenge is to make a rapid and correct differential diagnosis among drug-induced pulmonary toxicity, tumour progression, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pneumonitis. While waiting for polymerase chain reaction (PCR) testing results, an accurate evaluation of the symptoms and serologic features can help us make a first diagnostic hypothesis and quickly start correct treatment. Physicians need a collaborative effort to develop and share a common database reporting clinical (anosmia, dysgeusia), serologic, and radiologic data in ICI-treated patients with lung cancer developing interstitial disease to create an evidence-based clinical diagnostic algorithm. This tool will continue to be helpful when we emerge from the pandemic crisis into a world in which COVID-19 may not have been eradicated to better select the target population requiring the most resource-consuming PCR tests.

Fears and Perception of the Impact of COVID-19 on Patients With Lung Cancer: A Mono-Institutional Survey.

In February 2020, Italy became one of the first countries to be plagued by the SARS-CoV-2 pandemic, COVID-19. In March 2020, the Italian government decreed a lockdown for the whole country, which overturned communication systems, hospital organization, and access to patients and their relatives and carers. This issue had a particular regard for cancer patients. Our Thoracic Oncology Division therefore reorganized patient access in order to reduce the risk of contagion and, at the same time, encourage the continuation of treatment. Our staff contacted all patients to inform them of any changes in treatment planning, check that they were taking safety measures, and ascertain their feelings and whether they had any COVID-19 symptoms. To better understand patients' fears and expectations of during the pandemic period, we created a nine-question interview, administered from April to May 2020 to 156 patients with lung cancer. Patients were classified by age, sex, comorbidity, disease stage, prior treatment, and treatment type. The survey showed that during the pandemic period some patients experienced fear of COVID-19, in particular: women (55% vs. 33%), patients with comorbidities (24% vs. 9%), and patients who had already received prior insult (radiotherapy or surgery) on the lung (30% vs. 11%). In addition, the patients who received oral treatment at home or for whom intravenous treatment was delayed, experienced a sense of relief (90% and 72% respectively). However, only 21% of the patients were more afraid of COVID-19 than of their cancer, in particular patients with long-term (> 12 months) vs. short-term cancer diagnosis (28% vs. 12.5%, respectively). Furthermore, the quarantine period or even just the lockdown period alone, worsened the quality of life of some patients (40%), especially those in oral treatment (47%). Our data demonstrate how lung cancer patients are more afraid of their disease than of a world pandemic. Also this interview indirectly highlights the clinician's major guiding principle in correctly and appropriately managing not just the patient's expectations of their illness and its treatment, but also and especially of the patient's fears.