Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed.

PURPOSE: The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. METHODS: The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). RESULTS: 1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27-85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1-17.9), median OS was 16.1 months (95% CI, 14.4-18.8) and PFS was 9.9 months (95% CI, 8.8-11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6-17.1). ORR was 43.4% (95% CI, 40.4-46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). CONCLUSIONS: First-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study.

Treatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go.

Recently, the fifth edition of the WHO classification recognized the thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) as a separate entity from conventional non-small cell lung cancer with SMARCA4 deficiency because of the different clinicopathological characteristics of these two diseases. SMARCA4-UT mainly occurs in young to middle-aged adults and involves a large mass compressing the tissues surrounding the mediastinum and lung parenchyma. Unfortunately, SMARCA4-UT shows a high probability of recurrence after upfront surgery as well as radiotherapy resistance; moreover, chemotherapy has low efficacy. Moreover, given the recent classification of SMARCA4-UT, no data concerning specific clinical trials are currently available. However, several case reports show immunotherapy efficacy in patients with this disease not only in a metastatic setting but also in a neoadjuvant manner, supporting the development of clinical trials. In addition, preclinical data and initial clinical experiences suggest that inhibiting pathways such as CDK4/6, AURKA, ATR, and EZH2 may be a promising therapeutic approach to SMARCA4-UT.

Comparison between vision transformers and convolutional neural networks to predict non-small lung cancer recurrence.

Non-Small cell lung cancer (NSCLC) is one of the most dangerous cancers, with 85% of all new lung cancer diagnoses and a 30-55% of recurrence rate after surgery. Thus, an accurate prediction of recurrence risk in NSCLC patients during diagnosis could be essential to drive targeted therapies preventing either overtreatment or undertreatment of cancer patients. The radiomic analysis of CT images has already shown great potential in solving this task; specifically, Convolutional Neural Networks (CNNs) have already been proposed providing good performances. Recently, Vision Transformers (ViTs) have been introduced, reaching comparable and even better performances than traditional CNNs in image classification. The aim of the proposed paper was to compare the performances of different state-of-the-art deep learning algorithms to predict cancer recurrence in NSCLC patients. In this work, using a public database of 144 patients, we implemented a transfer learning approach, involving different Transformers architectures like pre-trained ViTs, pre-trained Pyramid Vision Transformers, and pre-trained Swin Transformers to predict the recurrence of NSCLC patients from CT images, comparing their performances with state-of-the-art CNNs. Although, the best performances in this study are reached via CNNs with AUC, Accuracy, Sensitivity, Specificity, and Precision equal to 0.91, 0.89, 0.85, 0.90, and 0.78, respectively, Transformer architectures reach comparable ones with AUC, Accuracy, Sensitivity, Specificity, and Precision equal to 0.90, 0.86, 0.81, 0.89, and 0.75, respectively. Based on our preliminary experimental results, it appears that Transformers architectures do not add improvements in terms of predictive performance to the addressed problem.

A CT-based transfer learning approach to predict NSCLC recurrence: The added-value of peritumoral region.

Non-small cell lung cancer (NSCLC) represents 85% of all new lung cancer diagnoses and presents a high recurrence rate after surgery. Thus, an accurate prediction of recurrence risk in NSCLC patients at diagnosis could be essential to designate risk patients to more aggressive medical treatments. In this manuscript, we apply a transfer learning approach to predict recurrence in NSCLC patients, exploiting only data acquired during its screening phase. Particularly, we used a public radiogenomic dataset of NSCLC patients having a primary tumor CT image and clinical information. Starting from the CT slice containing the tumor with maximum area, we considered three different dilatation sizes to identify three Regions of Interest (ROIs): CROP (without dilation), CROP 10 and CROP 20. Then, from each ROI, we extracted radiomic features by means of different pre-trained CNNs. The latter have been combined with clinical information; thus, we trained a Support Vector Machine classifier to predict the NSCLC recurrence. The classification performances of the devised models were finally evaluated on both the hold-out training and hold-out test sets, in which the original sample has been previously divided. The experimental results showed that the model obtained analyzing CROP 20 images, which are the ROIs containing more peritumoral area, achieved the best performances on both the hold-out training set, with an AUC of 0.73, an Accuracy of 0.61, a Sensitivity of 0.63, and a Specificity of 0.60, and on the hold-out test set, with an AUC value of 0.83, an Accuracy value of 0.79, a Sensitivity value of 0.80, and a Specificity value of 0.78. The proposed model represents a promising procedure for early predicting recurrence risk in NSCLC patients.

Safety evaluation of immune checkpoint inhibitors combined with chemotherapy for the treatment of small cell lung cancer: A meta-analysis of randomized controlled trials.

BACKGROUND: The addition of immune checkpoint inhibitors (ICIs) to chemotherapy is the new standard of care in the first-line treatment of small cell lung cancer (SCLC). However, although the concomitant use of immunotherapy and chemotherapy can increase the antitumor efficacy, it can also increase toxicity. The present study evaluated the tolerability of immune-based combinations in the first-line treatment of SCLC. METHODS: Relevant trials were identified by searching electronic databases and conference meetings. Seven phase II and III randomized controlled trials and 3766 SCLC patients were included in the meta-analysis (immune-based combinations = 2133; chemotherapy = 1633). Outcomes of interest included treatment-related adverse events (TRAEs) and the rate of discontinuation due to TRAEs. RESULTS: Immune-based combination treatment was associated with a higher risk of grade 3-5 TRAEs (odds ratio [OR], 1.16; 95% confidence interval [CI]: 1.01-1.35). Immune-based combinations were associated with a higher risk of TRAEs leading to discontinuation (OR, 2.30; 95% CI: 1.17-4.54). No differences were observed in grade 5 TRAEs (OR, 1.56; 95% CI: 0.93-2.63). CONCLUSION: This meta-analysis indicates that the addition of immunotherapy to chemotherapy in SCLC patients is associated with a higher risk of toxicity and probably of treatment discontinuation. Tools for identifying SCLC patients that would not benefit from immune-based therapy are urgently needed.

Immunotherapy in Elderly Patients Affected by Non-Small Cell Lung Cancer: A Narrative Review.

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers, and most NSCLC is diagnosed in the advanced stage. The advent of immune check point inhibitors (ICIs) changed the therapeutic scenario both in metastatic disease (in first and subsequent lines) and earlier settings. Comorbidities, reduced organ function, cognitive deterioration, and social impairment give reasons for a greater probability of adverse events, making the treatment of elderly patients challenging. The reduced toxicity of ICIs compared to standard chemotherapy makes this approach attractive in this population. The effectiveness of ICIs varies according to age, and patients older than 75 years may benefit less than younger patients. This may be related to the so-called immunosenescence, a phenomenon that refers to the reduced activity of immunity with older age. Elders are often under-represented in clinical trials, even if they are a large part of the patients in a clinical practice. In this review, we aim to explore the biological aspects of immunosenescence and to report and analyze the most relevant and recent literature findings on the role of immunotherapy in elderly patients with NSCLC.

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy.

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented. Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy. Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027). Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation.

An Update on the Role of Anti-EGFR in the Treatment of Older Patients with Metastatic Colorectal Cancer.

Although colorectal cancer is increasingly being diagnosed in older patients, their number is largely underrepresented in phase II or III clinical trials. Consequently, guidelines and the SIOG recommendations are not sufficiently clear regarding the treatment of these patients, particularly when chemotherapy is combined with monoclonal antibodies (bevacizumab, cetuximab, and panitumumab). Targeted therapy based on the use of anti-epidermal growth factor receptors (EGFRs) is conditioned by the potential for increased toxicity, making it more difficult to treat an older, rat sarcoma virus (RAS) and B rapidly accelerated fibrosarcoma (BRAF) wild-type patient. In light of a more detailed characterization of the older population, modernly differentiable between fit, vulnerable, or frail patients on the basis of the comprehensive geriatric assessment, and of the analysis of more recent studies, this review fully collects data from the literature, differentiating the results on functional status patients.

Pralsetinib in RET fusion-positive non-small-cell lung cancer: A real-world data (RWD) analysis from the Italian expanded access program (EAP).

OBJECTIVES: The selective RET-inhibitor pralsetinib has shown therapeutic activity in early clinical trials in patients with non-small cell lung cancer (NSCLC) harboring rearranged during transfection (RET) gene fusions. To date, the real-world efficacy of pralsetinib in this population is unknown. MATERIALS AND METHODS: A retrospective efficacy and safety analysis was performed on data from patients with RET-fusion positive NSCLC enrolled in the pralsetinib Italian expanded access program between July 2019 and October 2021. RESULTS: Overall, 62 patients with RET-fusion positive NSCLC received pralsetinib at 20 Italian centers. Next-generation sequencing was used to detect RET alterations in 44 patients (73 %). The most frequent gene fusion partner was KIF5B (75 % of 45 evaluable). Median age was 62 years (range, 36-90), most patients were female (57 %) and never smokers (53 %). Brain metastases were known in 18 patients (29.5 %) at the time of pralsetinib treatment. 13 patients were treatment naïve (unfit for chemotherapy), 48 were pretreated (median number of previous lines: 1, range, 1-4). The objective response rate (ORR) was 66 % [95 % confidence interval (CI), 53-81] in the evaluable population (n = 59). The disease control rate (DCR) was 79 %. After a median follow-up of 10.1 months, the median progression free survival was 8.9 months (95 %CI, 4.7-NA). In patients with measurable brain metastases (n = 6) intracranial ORR was 83 %, intracranial DCR was 100 %. Overall, 83.6 % of patients experienced any-grade treatment-related adverse events (TRAEs), 39 % grade 3 or greater (G ≥ 3). The most common G ≥ 3 TRAEs were neutropenia (9.8 %), dry mouth/oral mucositis (8.2 %), and thrombocytopenia (6.6 %). Seven patients (12 %) discontinued pralsetinib due to TRAEs, twenty-six had at least one dose level modification due to TRAEs. Two treatment-related deaths were observed (1 sepsis, 1 typhlitis). CONCLUSIONS: In the real-world setting, pralsetinib confirmed durable systemic activity and intracranial response in RET-fusion positive NSCLC. Toxicity profile was consistent with previous reports.

Prognostic factors for survival in extensive-stage small cell lung cancer: An Italian real-world retrospective analysis of 244 patients treated over the last decade.

BACKGROUND: Potential relationships with the prognosis of patients with extensive-stage non-small cell lung cancer (ES-SCLC) have been investigated without valid results. METHODS: A retrospective analysis of real-world data of consecutive patients with ES-SCLC admitted to our Medical Thoracic Oncology Unit was carried out from 2010 to 2020, focusing on identification of prognostic factors. Kaplan-Meier analysis was used to represent progression-free survival (PFS) and overall survival (OS). Univariable and multivariable Cox models were used to investigate prognostic factors. RESULTS: The analysis included 244 patients. The median OS was 8 months (95% confidence interval [CI]: 8-10) and the median PFS was 5 months (95% CI: 5-6). The univariable analysis showed that factors associated with shorter OS were older age (p = 0.047), TNM stage 4 versus 3 (p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 and 2 versus 0 (p < 0.001), and >2 metastatic sites (p = 0.004). Mediastinal radiotherapy (RT) (p < 0.001), >1 irradiated site (p = 0.026), 3 and 4 chemotherapy (CT) lines versus 1 (p = 0.044 and 0.001, respectively), prophylactic cranial irradiation (PCI) (p < 0.001), and surgery (p = 0.001) correlated with longer OS. The multivariable analysis revealed statistically significant associations for TNM, ECOG PS 2 versus 0, number of CT lines, PCI, and surgery. A total of 23 patients (9.4%) survived ≥24 months, 39% of whom had received four CT lines and 48% had mediastinal RT. CONCLUSIONS: Our data suggest that tumor burden, PS, and mediastinal RT strongly correlate with outcome. With the addition of immunotherapy to CT, the identification of new biomarkers as predictive factors is urgently required.

Controversial role of mast cells in NSCLC tumor progression and angiogenesis.

Mast cells (MCs) are multifunctional immune cells implicated in both physiological and pathological processes. Among the latter, MCs play a crucial role in cancer. Many studies have shown a correlation between MCs and tumor progression in several solid and hematological malignancies. In particular, MCs can directly promote tumor growth via c-kit/stem cell factor-dependent signaling and via the release of histamine, which modulate tumor growth through H1 and H2 receptors. At the same time, MCs can increase tumor progression by stimulating angiogenesis via both proangiogenic cytokines stored in their cytoplasm, and by acting on the tumor microenvironment and extracellular matrix. With regard to NSCLC, the role of MCs has not yet been established, with studies showing a correlation with a poor prognosis on the one hand and suggesting a protective effect of MCs on the other hand. These controversial evidences are at least, in part, due to the heterogeneity of the studies exploring the role of MCs in NSCLC, with some studies describing only the MC count without specification of the activation and degranulation state, and without reporting the intratumoral localization and the proximity to other immune and cancer cells. A better knowledge of the role of MCs in NSCLC is mandatory, not only to define their prognostic and predictive proprieties but also because targeting them could be a possible therapeutic strategy.

Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples.

BACKGROUND: According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples. METHODS: For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test. RESULTS: HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. CONCLUSIONS: HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018.

Understanding the lived experience of lung cancer: a European social media listening study.

BACKGROUND: Social media platforms are increasingly being used by stakeholders to generate, access, and share health-related information and experiences. Lung cancer is the most common cancer, impacting > 2 million patients globally. This observational study utilized a social listening approach to analyze social media trends and gain insights into stakeholder perceptions of lung cancer. METHODS: This social media study retrospectively collated data from open access blogs, forums, and social networking sites. Social media posts were collected between June 2019-May 2020 from 14 European countries. Using social media aggregator tools, posts comprising lung cancer and non-small cell lung cancer-specific terms were extracted. Manual and automated relevancy algorithms filtered the extracted information to provide the relevant dataset. This contextualized dataset was further mined to generate the final data for analysis. RESULTS: Of 1360 conversations analyzed, 42% were generated by patients/caregivers and 14% by healthcare professionals (HCPs). A majority of patients were 51-70 years old (approximately 50%) and 91% (n = 500/550) had late-stage cancer. Treatment (35%) and disease awareness (30%) were among the most discussed topic of the patient journey. Although the overall treatment sentiment was neutral, chemotherapy was the treatment type with the highest associated negative sentiment (28%); fewer negative sentiments were associated with immunotherapy (9%) and targeted therapy (2%), due to perceptions of longer survival outcomes and fewer side effects. In conversations that discussed clinical endpoints, "survivability" and "overall survival" (47 and 30%, respectively; n = 539) were most frequently mentioned by stakeholders. HCPs mostly used technical terms, whereas patients and caregivers used colloquial terms such as "getting rid of cancer". Emotional wellness was identified to have a huge impact on quality of life in lung cancer. Delay or treatment cancellations due to COVID-19, lack of effective treatments and funding, and lack of empathy by physicians emerged as the key unmet needs among patients/caregivers. CONCLUSIONS: Social listening proved to be an effective tool to explore stakeholders' perceptions and their key unmet needs, typically not available in published literature or databases, and provides HCPs with valuable insights into the distress, doubts, and needs of lung cancer patients and caregivers.

Informative Power Evaluation of Clinical Parameters to Predict Initial Therapeutic Response in Patients with Advanced Pleural Mesothelioma: A Machine Learning Approach.

Malignant pleural mesothelioma (MPM) is a rare neoplasm whose early diagnosis is challenging and systemic treatments are generally administered as first line in the advanced disease stage. The initial clinical response may represent a useful parameter in terms of identifying patients with a better long-term outcome. In this report, the initial therapeutical response in 46 patients affected with advanced/unresectable pleural mesothelioma was investigated. The initial therapeutic response was assessed by CT scan and clinical examination after 2-3 treatment cycles. Our preliminary evaluation shows that the group of patients treated with regimens including antiangiogenetics and/or immunotherapy had a significantly better initial response as compared to patients only treated with standard chemotherapy, exhibiting a disease control rate (DCR) of 100% (95% IC, 79.40-100%) and 80.0% (95% IC, 61.40-92.30%), respectively. Furthermore, the therapeutic response was correlated with the disease stage, blood leukocytes and neutrophils, high albumin serum levels, and basal body mass index (BMI). Specifically, the patients with disease stage III showed a DCR of 95.7% (95% IC, 78.1-99.9%), whereas for disease stage IV the DCR decreased to 66.7% (95% IC, 34.9-9.1%). Moreover, a better initial response was observed in patients with a higher BMI, who reached a DCR of 96.10% (95% IC, 80.36-99.90%). Furthermore, in order to evaluate in the predictive power of the collected features a multivariate way, we report the preliminary results of a machine learning model for predicting the initial therapeutic response. We trained a state-of-the-art algorithm combined to a sequential forward feature selection procedure. The model reached a median AUC value, accuracy, sensitivity, and specificity of 77.0%, 75%, 74.8%, and 83.3%, respectively. The features with greater informational power were gender, histotype, BMI, smoking habits, packs/year, and disease stage. Our preliminary data support the possible favorable correlation between innovative treatments and therapeutic response in patients with unresectable/advanced pleural mesothelioma. The small sample size does not allow concrete conclusions to be drawn; nevertheless, this work is the basis of an ongoing study that will also involve radiomics in a larger dataset.

What Are the Biomarkers for Immunotherapy in SCLC?

Small-cell lung cancer (SCLC) is an aggressive malignancy that exhibits a rapid doubling time, a high growth fraction, and the early development of widespread metastases. The addition of immune checkpoint inhibitors to first-line chemotherapy represents the first significant improvement of systemic therapy in several decades. However, in contrast to its effects on non-SCLC, the advantageous effects of immunotherapy addition are modest in SCLC. In particular, only a small number of SCLC patients benefit from immune checkpoint inhibitors. Additionally, biomarkers selection is lacking for SCLC, with clinical trials largely focusing on unselected populations. Here, we review the data concerning the major biomarkers for immunotherapy, namely, programmed death ligand 1 expression and tumour mutational burden. Furthermore, we explore other potential biomarkers, including the role of the immune microenvironment in SCLC, the role of genetic alterations, and the potential links between neurological paraneoplastic syndromes, serum anti-neuronal nuclear antibodies, and outcomes in SCLC patients treated with immunotherapy.

Psychological well-being in cancer outpatients during COVID-19.

PURPOSE: The psychological status of cancer outpatients receiving anti-neoplastic treatment during the lockdown in a Italian non-COVID Cancer Center, was been investigated with the following aims: to measure the levels of post-traumatic stress symptoms, depression and anxiety; to compare patients with different cancer sites; to compare the anxiety and depression levels measured in this emergency period between cancer and non-cancer patients and between cancer patients before and after the emergency. METHODS: The following questionnaires were used: The Hospital Anxiety and Depression Scale (HADs) and the Impact of Event Scale-Revised (IES-R).Worries regarding the COVID-19 on patients' lives, socio-demographic and clinical details were collected using a brief structured questionnaire. RESULTS: One-hundred seventy-eight outpatients were enrolled. We found that 55% of patients were above the cut-off for HADS general scale and 23.7% had severe level of PTSD. The 68% of patients declared that their worries have increased during the pandemic especially for women. Patients with lung cancer have higher general distress compared with patients with breast cancer and lymphoma. The non cancer sample had values significantly higher both for the IES-R scales and for HADS Depression subscale. Finally, cancer patients who experienced the health emergency showed higher levels of anxiety than those measured 2 years ago. CONCLUSION: Cancer out-patients of the present sample have severe post-traumatic stress symptoms and psychological distress, those with lung cancer are at higher risk and may need special attention. Non-oncological subjects have higher depression levels than cancer patients.

Exploring the role of respiratory microbiome in lung cancer: A systematic review.

Giving the potential contribute in cancer initiation and progression, lung microbiota represents a promising topic in cancer research, although still unexplored. We performed a systematic literature search to identify clinical studies evaluating lung microbiota composition, its correlation with lung cancer patients' clinico-pathological features and prognosis. Of the identified 370 studies, 21 were eligible and included. Although studies were heterogeneous, lung cancer resulted to be enriched in peculiar microbial communities, with differences in composition and diversity according to clinico-pathological parameters. Few studies explored how lung microbiota influences cancer outcome. In light of these findings and borrowing the suggestions coming from gut microbiota, we speculate that respiratory microbiome may influence pathogenesis, progression and outcome of lung cancer. Taking advantage of the experience of chronical lung diseases, prospective studies should be designed to evaluate lung microbiota changes throughout any phase of lung cancer course, particularly with the advent of immunotherapy as pivotal treatment.

Successful treatment of triple EGFR mutation T785A/L861Q/H297_E298 with afatinib.

Patients with non-small cell lung cancer (NSCLC) and uncommon epidermal growth factor receptor (EGFR) mutation are characterized by high heterogeneity, and globally considered to have a worse prognosis than patients with the two common mutations; exon 19 deletion, and exon 21 L858R. Nevertheless, some uncommon mutations do confer sensitivity to tyrosine kinase inhibitors (TKIs) which is comparable with common mutations. In particular, some compound EGFR mutations seem to be characterized by a favorable prognosis. Unfortunately, the rarity of complex EGFR mutations results in difficult clinical decision-making. Herein, to the best of our knowledge, we report the first case of an NSCLC patient with an EGFR triple mutation containing T785A/L861Q/H297_E298 who was successfully treated with afatinib.

[RET rearrangements in advanced lung cancer: a target to always look for.] / Riarrangiamenti di RET nelle neoplasie polmonari : quando è bene insistere nella ricerca di oncodriver.

Introduction . RET rearrangements have been recently aroused growing interest, due to the availability of target therapies increasingly active and safe. The search for these oncogenic alterations in patients with advanced lung adenocarcinoma has become an integral part of the biomolecular tumoral assessment, in order to possibly provide a selective therapeutical option also for rare subgroups of patients, but belonging to lung cancer that is considered a "big killer", representing the most frequent cause of cancer-related death worldwide. Following to the introduction of modern biomolecular techniques, such as the comprehensive genome profiling (CGP), that has been added to the immunohistochemistry (IHC) and the "in situ fluorescent ibridation" (FISH), the availability of techniques based on genomic sequencing such as the next generation sequencing (NGS), achievable either on tumoral tissue or on plasma, has made it easier to identify oncogenic alterations that, although rare, are potentially treatable with molecularly targeted drugs. A complete molecular assessment should preferable be obtained at the first diagnosis, in order not to neglect the possibility of using target drugs if indicated, but it is possible and desiderable to complete or to re-determine the biomolecular profile also during the clinical course, due to the possibility of spontaneous or drug-induced resistance mechanisms that can modify the biomolecular tumoral characteristics; this reassessment is achievable both through tissutal rebiopsy and by plasma test, the so-called "liquid biopsy". Clinical case . In this report, we describe the case of a patient with advanced lung adenocarcinoma, pretreated with multiple chemo- and immuno-therapic lines of treatment; at baseline, the biomolecular profile was not complete, as well as during the clinical course through repeated re-biopsies. Conclusions . At the time of further disease progression, a liquid biopsy with NGS revealed the presence of a RET rearrangement. This clinical case underscores the importance of a complete biomolecolar assessment in order to identify target linked to effective and innovative treatment options; it is also highlighted the usefulness of the modern CGP techniques, applicable to tumoral tissue and plasma.