Small-Cell Lung Cancer: Is Liquid Biopsy a New Tool Able to Predict the Efficacy of Immunotherapy?

Small-cell lung cancer (SCLC) cases represent approximately 15% of all lung cancer cases, remaining a recalcitrant malignancy with poor survival and few treatment options. In the last few years, the addition of immunotherapy to chemotherapy improved clinical outcomes compared to chemotherapy alone, resulting in the current standard of care for SCLC. However, the advantage of immunotherapy only applies to a few SCLC patients, and predictive biomarkers selection are lacking for SCLC. In particular, due to some features of SCLC, such as high heterogeneity, elevated cell plasticity, and low-quality tissue samples, SCLC biopsies cannot be used as biomarkers. Therefore, the characterization of the tumor and, subsequently, the selection of an appropriate therapeutic combination may benefit greatly from liquid biopsy. Soluble factors, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) are now useful tools in the characterization of SCLC. This review summarizes the most recent data on biomarkers detectable with liquid biopsy, emphasizing their role in supporting tumor detection and their potential role in SCLC treatment choice.

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.

Feasibility of cabazitaxel in octogenarian prostate cancer patients.

Background: To evaluate the effectiveness and safety of cabazitaxel in castration-resistant prostate cancer patients aged ≥80 years, we performed a retrospective study on a sample of patients from 11 Italian cancer centers. Materials and methods: Fifty-seven patients aged ≥80 years were treated with cabazitaxel after previous failure with docetaxel; 39 completed a comprehensive geriatric assessment questionnaire (34 fit and 5 vulnerable) and 8 patients (14%) had an Eastern Cooperative Oncology Group performance status (PS) ≥2, while most had a PS of 0-1 (86%). Cabazitaxel was administered at a dose of 25 mg/m2 in 30 (52%) patients and 20 mg/m2 or adapted schedules in 27 (48%) patients. These schedules were adopted mainly in patients ≥85 years (75%), with a PS ≥2 (87.5%), and those classified as vulnerable (100%). Results: The duration of treatment was 4.8 months and was comparable in all subgroups; disease control rate was reported in 36 patients (63%); prostate-specific antigen response was recorded in 18 patients (31.5%). Median overall survival was 13.1 months regardless of age (<85/≥85 years), but overall survival was reduced in vulnerable (7.2 months) and PS ≥ 2 patients (6.8 months). The most frequently documented grade 3-4 toxicities were neutropenia (14%) and diarrhea (10.5%). Six patients (10.5%) dropped out due to severe toxicity. Conclusions: Octogenarian patients can be treated with cabazitaxel with reduced doses or alternative schedules that are associated with less toxicity and fewer treatment interruptions. Comprehensive geriatric assessment could facilitate more appropriate patient selection.

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.

Neutrophil-to-Lymphocyte Ratio Is a Major Prognostic Factor in Non-small Cell Lung Carcinoma Patients Undergoing First Line Immunotherapy With Pembrolizumab.

BACKGROUND/AIM: Lung cancer is one of the most common malignant neoplastic diseases and by far the leading cause of cancer death worldwide. Recently, immune checkpoint inhibitors (ICIs) have received increasing attention for playing a crucial role in non-small cell lung cancer (NSCLC). Biomarkers, such as programmed cell death-ligand 1 (PD-L1) and tumor mutational burden (TMB), seemed to be helpful in selecting patients who are more likely to benefit from ICI treatment: however, their role has not yet been fully clarified. PATIENTS AND METHODS: In this retrospective study, we evaluated the relationship between pre-treatment peripheral blood neutrophil-to-lymphocyte ratio (NLR) and survival in 252 patients suffering from advanced NSCLC who had received pembrolizumab as their first-line immunotherapy. RESULTS: Compared to their NLR low counterparts who had a median overall survival (OS) of 34.8 months, patients with NLRs above 4.8 had a median OS of 7.6 months (HR=3.26, 95%Cl=2.3-4.6, p-value<0.0000001). In multivariate Cox regression analysis, alongside other variables, such as metastatic sites, age, and sex, NLR and PD-L1 predicted progression-free survival and OS; furthermore, a very high NLR - over 10 - seemed to forecast a very dismal prognosis in patients undergoing immunotherapy, with sudden deaths in the days immediately following therapy (median OS=3.8 months). CONCLUSION: NLR acts as a valuable and reliable prognostic factor in non-small cell lung carcinoma patients undergoing first line immunotherapy with pembrolizumab. Additional investigation is necessary to fully elucidate the underlying biological rationale, which can be found in myeloid derived suppressor cells, a heterogeneous population of cells with neutrophil-like immunophenotypic features.

circPVT1 and PVT1/AKT3 show a role in cell proliferation, apoptosis, and tumor subtype-definition in small cell lung cancer.

Small cell lung cancer (SCLC) is treated as a homogeneous disease, although the expression of NEUROD1, ASCL1, POU2F3, and YAP1 identifies distinct molecular subtypes. The MYC oncogene, amplified in SCLC, was recently shown to act as a lineage-specific factor to associate subtypes with histological classes. Indeed, MYC-driven SCLCs show a distinct metabolic profile and drug sensitivity. To disentangle their molecular features, we focused on the co-amplified PVT1, frequently overexpressed and originating circular (circRNA) and chimeric RNAs. We analyzed hsa_circ_0001821 (circPVT1) and PVT1/AKT3 (chimPVT1) as examples of such transcripts, respectively, to unveil their tumorigenic contribution to SCLC. In detail, circPVT1 activated a pro-proliferative and anti-apoptotic program when over-expressed in lung cells, and knockdown of chimPVT1 induced a decrease in cell growth and an increase of apoptosis in SCLC in vitro. Moreover, the investigated PVT1 transcripts underlined a functional connection between MYC and YAP1/POU2F3, suggesting that they contribute to the transcriptional landscape associated with MYC amplification. In conclusion, we have uncovered a functional role of circular and chimeric PVT1 transcripts in SCLC; these entities may prove useful as novel biomarkers in MYC-amplified tumors.

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.

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.

Gender Differences and Immunotherapy Outcome in Advanced Lung Cancer.

In developed countries, lung cancer is the leading cause of cancer-related death in both sexes. Although cigarette smoking represents the principal risk factor for lung cancer in females, the higher proportion of this neoplasm among non-smoking women as compared with non-smoking men implies distinctive biological aspects between the two sexes. Gender differences depend not only on genetic, environmental, and hormonal factors but also on the immune system, and all these aspects are closely interconnected. In the last few years, it has been confirmed that the immune system plays a fundamental role in cancer evolution and response to oncological treatments, specifically immunotherapy, with documented distinctions between men and women. Consequently, in order to correctly assess cancer responses and disease control, considering only age and reproductive status, the results of studies conducted in female patients would probably not categorically apply to male patients and vice versa. The aim of this article is to review recent data about gender disparities in both healthy subjects' immune system and lung cancer patients; furthermore, studies concerning gender differences in response to lung cancer immunotherapy are examined.

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.

Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

INTRODUCTION: The impact of cancer on basal fertility and ovarian response to stimulation has not yet been clarified. Evidence on this topic is scarce and conflicting. Aim of this study was to assess the impact of breast cancer stage and grade on the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation. METHODS: Retrospective cohort study evaluating data on 101 stimulation cycles of women with breast cancer undergoing oocyte cryopreservation categorized according to breast cancer stage (low-stage: I; high-stage:II-III) and grade (low-grade: G1-2; high-grade: G3) using the American Joint Committee on Cancer staging system (VIII edition). RESULTS: High-stage disease was not associated with worse oocyte retrieval outcomes (median 7 vs 7, p = 0.75). High-grade disease patients showed a significantly lower antral follicle count (AFC) compared to low-grade disease patients (10 vs 13, p = 0.03), and required higher doses of FSH (2612 IU vs 2250 IU; p = 0.03) during stimulation. Median number of vitrified oocytes was 6 in low-grade disease patients and 7 in high-grade disease patients (p = 0.35). CONCLUSIONS: Stage and grade of breast cancer do not impact the number of retrieved mature oocytes. However, higher grade of breast cancer is associated with lower AFC at baseline and need for higher doses of gonadotropin during ovarian stimulation.

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.

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.

[Efficacy of pralsetinib in a patient with advanced lung adenocarcinoma positive for RET rearrangement: the importance of Comprehensive Genomic Profiling.] / Efficacia di pralsetinib in un paziente con adenocarcinoma polmonare in stadio avanzato positivo per riarrangiamento di RET: l'importanza del Comprehensive Genomic Profiling.

Modern gene profiling techniques have allowed in recent years considerable progresses in the knowledge of molecular alterations in the context of non-small cell lung cancer (NSCLC). In some cases, these alterations have been recognized as having a pathogenic role and targeted therapies capable of inhibiting tumor proliferation by selective and specific blocking of the enzymatic activity of the related abnormal proteins have been developed. This has made it possible to improve the effectiveness of the treatments by minimizing toxicity. Today it is essential to apply Comprehensive Genomic Profiling methods also in clinical practice, in order to allow the best treatment available for each patient, possibly also in the context of clinical trials. Below we report the clinical history of a patient with advanced stage adenocarcinoma of the lung with molecular diagnosis of RET fusion, treated with pralsetinib with excellent clinical and radiological response and good tolerability. This clinical case emphasizes the importance of the broader molecular profiling in patients with advanced NSCLC (especially for non-squamous histology) from the diagnosis before starting first-line treatment.

Smoking Prevalence, Knowledge and Perceptions on Tobacco Control Among Healthcare Professionals: A Survey in an Italian Cancer Center.

Smoking is recognized as the major cause of lung cancer. Healthcare professionals play an important role in lung cancer prevention policies, as they act as a source of guidance for patients and advocates. The following survey evaluated prevalence, knowledge, and attitudes toward tobacco smoking among a sample of workers in "IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, an Italian cancer hospital. An anonymous questionnaire was completed by 104 healthcare professionals to collect personal and occupational data about smoking status, knowledge about the harms of smoking, current legislation in place, Second-Hand Smoke (SHS) awareness, and, for ex-smokers, the reasons for quitting. Among participants, 17.8% were current smokers, 26.2% former smokers, and 56% never smoked. Only 40% acknowledged that the smoking ban is generally respected, and 63.2% reported that they smoke during working hours. Most of the participants perceived tobacco control policy as an efficient way to protect public health. Currently, the implementation of Italian anti-smoking legislation has so far improved neither smoking cessation rates nor the will to quit smoking completely. Our experience highlights that to date the anti-smoking strategies have limited efficacy even in a cancer center; in fact, there is still a large prevalence of smokers among hospital personnel. Therefore, it is strongly suggested that interventions be shared with all healthcare workers, specifically aimed at developing a culture of health promotion.

Impact of tobacco control interventions on smoking initiation, cessation, and prevalence: a systematic review.

This article investigates the effects of tobacco control policies on smoking initiation, cessation and prevalence by examining the papers published in the last 5 years. Twenty-one articles have been selected by two authors and sorted by four types of tobacco control: tobacco prices, anti-smoking campaigns for young people, mass media intervention and public smoking bans. Price/tax increase has deterrent effect on smoking initiation but does not promote smoking cessation; intervention on young people could reduce the smoking initiation if carried out at an early age and if acted on social skills and with peer-led approach, as opposed to restraining measures which hare generally easily circumvented by young people. The mass media campaigns showed positive effect on attempts to quit among smokers if carried forward over time and by involving multiple communication channels (TV, internet, radio). The bans in public have little effect on smoking cessation but could improve the overall well-being of non-smokers. Heterogeneous results have been described by different studies probably because of different research methodologies, cultural aspects and the really effective implementation of the rules for each country. In conclusion, comprehensive tobacco control interventions to reduce smoking prevalence and modify the smoking behavior are recommended. Moreover, the use of e-cigarettes and heat-not-burn (HnB) products, as possible helping tool for smoke cessation, currently remains controversial.