Immune checkpoint inhibitors and Carbon iON radiotherapy In solid Cancers with stable disease (ICONIC).

ICONIC is a multicenter, open-label, nonrandomized phase II clinical trial aiming to assess the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. The primary end point is objective response rate, and the secondary end points are safety, survival and disease control rate. Translational research is an exploratory aim. The planned sample size is 27 patients. The study combination will be considered worth investigating if at least four objective responses are observed. If the null hypothesis is rejected, ICONIC will be the first proof of concept of the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in oncology.

ICONIC is a multicenter, open-label, nonrandomized, phase II clinical trial aiming to evaluate the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. Considering that no clinical trials have been conducted thus far to assess the safety of the association between immune checkpoint inhibitors and carbon ion radiotherapy, the current clinical study will provide controlled data about the safety of this unprecedented therapeutic combination. Clinical Trial Registration: NCT05229614 (ClinicalTrials.gov).

The contingent equilibrium during imbalanced volcano tourism demand through fee estimation: An empirical analysis of tourism in Mount Etna.

Volcanic sites can be considered strategic areas for conservation and protection policies, but such policies may involve considerable costs However, not only are volcanic sites often integral to the tourism industry and, hence, of potential significant benefit to local economies in general; entrance fee income from tourists can also contribute to management and conservation costs in particular. Nevertheless, seasonal variations in tourism demand, resulting in over-and under-tourism situations, may impact on both the level of income generated as well as on the sustainability of sites Therefore, based on a case study of Mt Etna in Italy, this study considers establishing appropriate entry fee levels for volcano areas. First, a logit model is applied to the relevant socio-demographic and site-specific variables. The entrance fees are estimated on visitors' willingness to pay and demand elasticity. Applying contingent valuation method (CVM), two groups of tourists (high and low season visitors) are identified and surveyed, with each group demonstrating different willingness to pay and elasticity levels. Rather than applying a single fee, different entrance fees for the two groups are found to generate a higher level of revenue for the park's economic equilibrium. In addition, the different entrance fees offer the potential to mitigate the peak effects of over-tourism and support demand during under-tourism, with clear sustainability consequences. The results, which confirm four hypotheses set about Mt. Etna, could facilitate decision-makers in determining a feasible balance between management costs, tourism demand characteristics and protection commitments.

Treatment of lung large cell neuroendocrine carcinoma.

Lung large cell neuroendocrine carcinoma (L-LCNEC) is a rare, aggressive, and difficult-to-treat tumor. It is classified as a neuroendocrine subtype of large cell lung carcinoma (LCLC) belonging to the non-small cell lung cancer (NSCLC) group, but it is also included in the neuroendocrine tumor (NET) group. Most of the available data related to its treatment derive from retrospective analyses or small case series. For patients with L-LCNEC, prognosis is generally very poor. In early stages (I-II-III), surgery is recommended but does not seem to be sufficient. Platinum-based adjuvant chemotherapy may be useful while the role of neoadjuvant chemotherapy is still not well defined. In patients with advanced L-LCNEC, the chemotherapy regimens used in SCLC still remain the standard of treatment, but results are not satisfactory. Due to their peculiar clinical and biological features and the lack of literature data, there is an emerging need for a consensus on the best treatment strategy for L-LCNEC and for the identification of new therapeutic options. In this review, we will discuss the key aspects of L-LCNEC management with the aim to clarify the most controversial issues.

Systemic lupus erythematosus reactivation after chemoimmunotherapy in preexisting autoimmune disease.

The use of immune checkpoint inhibitors (ICIs) offers new possibilities in modern treatment of many types of cancers. Few data regarding safety and efficacy of ICIs are available, and are mainly from retrospective studies and case reports rather than from clinical trials, in the context of preexisting autoimmune disease, mainly due to the risk of severe toxicity. We present an unexpected life-threatening reactivation of systemic lupus erythematosus after one dose of chemo-immunotherapy with pembrolizumab for oligometastatic non-small-cell lung cancer. We analyze data coming from the published literature in this setting and discuss the risk-benefit balance of immunotherapy in patients with preexisting severe autoimmune disease.

Paraneoplastic neurological syndromes in patients affected by SCLC: a case series.

Paraneoplastic syndromes occur in about 0.1% of patients affected by neoplastic diseases. In some types of tumors, such as Small Cell Lung Cancer (SCLC), Thymoma, and particular forms of Plasmacytoma, the association with Paraneoplastic Neurological Syndromes (PNS) is much more frequent. It seems that these syndromes are triggered by tumor production of factors normally expressed only by the individual's nervous system. The immune system stimulates an autoimmune response against these factors that induce neurological symptoms. Also, in light of the latest updates on the relationship between immunotherapy and PNS as well as of the introduction of first-line immunotherapy in SCLC, it seems that the use of immunotherapy in SCLC is associated with concomitant increase in autoimmune neurological syndromes.In this article, we report our experience at Istituto Nazionale Tumori of Milan with three patients affected by SCLC and PNS. Our experience seems to confirm that the oncological treatment scarcely impacts the paraneoplastic neurological deficits. Further research is needed to improve the treatment and recovery of patients affected by PNS.

Efficacy of mRNA anti-SARS-CoV-2 vaccination and dynamics of humoral immune response in patients with solid tumors: results from the institutional registry of an Italian tertiary cancer center.

Background: Systemic immunosuppression characterizing cancer patients represents a concern regarding the efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, and real-world evidence is needed to define the efficacy and the dynamics of humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines. Methods: We conducted an observational study that included patients with solid tumors who were candidates for mRNA anti-SARS-CoV-2 vaccination at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. The primary objective was to monitor the immunologic response to the mRNA anti-SARS-CoV-2 vaccination in terms of anti-spike antibody levels. All the patients received two doses of the mRNA-1273 vaccine or the BNT162b2 vaccine. Healthcare workers served as a control group of healthy subjects. Results: Among the 243 patients included in the present analysis, 208 (85.60%) and 238 (97.94%) resulted seroconverted after the first and the second dose of vaccine, respectively. Only five patients (2.06%) had a negative titer after the second dose. No significant differences in the rate of seroconversion after two vaccine doses were observed in patients as compared with the control group of healthy subjects. Age and anticancer treatment class had an independent impact on the antibody titer after the second dose of vaccination. In a subgroup of 171 patients with available data about the third timepoint, patients receiving immunotherapy with immune checkpoint inhibitors seem to have a higher peak of antibodies soon after the second dose (3 weeks after), but a more pronounced decrease at a late timepoint (3 months after). Conclusions: The systemic immunosuppression characterizing cancer patients did not seem to dramatically affect the humoral response to anti-SARS-CoV-2 mRNA vaccines in our population of patients with solid tumors. Further investigation is needed to dissect the interplay between immunotherapy and longitudinal dynamics of humoral response to mRNA vaccines, as well as to analyze the cellular response to mRNA vaccines in cancer patients.

Parents' attitudes and behaviours towards recommended vaccinations in Sicily, Italy.

BACKGROUND: Since a long time, Italy has maintained a dual system to administer childhood immunisations, that is a certain number of mandatory vaccinations and a number of recommended vaccinations. The study aimed to explore the issues surrounding parental acceptance or non-acceptance of the recommended vaccinations for children. METHODS: Parents of children aged 3-5 years of day-care centres in Sicily were asked to fill out an anonymous questionnaire. Determinants of the attitude towards recommended vaccinations and social influence on the decision-making process were assessed using logistic regression analysis. RESULTS: Of the 1,500 selected parents, 81.0% participated in the study. Prior to the survey, the majority of children (97.6%) received recommended vaccines. Most parents (74.4%) received information about vaccinations from Family Paediatricians, showed a good knowledge about the side effects of the vaccines (73.1%), did not worry about their potential dangerousness (53.0%) and would have accepted their children to be vaccinated even if it was not required for day care (84.1%). The majority (79.9%) were not disposed to follow the advises of the anti-vaccination movements. Parents' background characteristics, sources of information and social influence were not significantly associated with parental acceptance of recommended vaccines for childhood. CONCLUSIONS: This study suggests that health information by Family Paediatricians is significantly associated with parental acceptance of recommended vaccinations.

Risk assessment of thromboembolic events in hospitalized cancer patients.

Hospitalized cancer patients are at increased risk for Thromboembolic Events (TEs). As untailored thromboprophylaxis is associated with hemorrhagic complications, the definition of a risk-assessment model (RAM) in this population is needed. INDICATE was a prospective observational study enrolling hospitalized cancer patients, with the primary objective of assessing the Negative Predictive Value (NPV) for TEs during hospitalization and within 45 days from discharge of low-grade Khorana Score (KS = 0). Secondary objectives were to assess KS Positive Predictive Value (PPV), the impact of TEs on survival and the development of a new RAM. Assuming 7% of TEs in KS = 0 patients as unsatisfactory percentage and 3% of as satisfactory, 149 patients were needed to detect the favorable NPV with one-sided α = 0.10 and power = 0.80. Stepwise logistic regression was adopted to identify variables included in a new RAM. Among 535 enrolled patients, 153 (28.6%) had a KS = 0. The primary study objective was met: 29 (5.4%) TEs were diagnosed, with 7 (4.6%) cases in the KS = 0 group (NPV = 95.4%, 95% CI 90.8-98.1%; one-sided p = 0.084). However, the PPV was low (5.7%, 95% CI 1.9-12.8%); a new RAM based on albumin (OR 0.34, p = 0.003), log(LDH) (OR 1.89, p = 0.023) and presence of vascular compression (OR 5.32, p < 0.001) was developed and internally validated. Also, TEs were associated with poorer OS (median, 5.7 vs 24.8 months, p < 0.001). INDICATE showed that the KS has a good NPV but poor PPV for TEs in hospitalized cancer patients. A new RAM was developed, and deserves further assessment in external cohorts.

Carcinomatosis under control by osimertinib in EGFR and TP53 mutated lung adenocarcinoma.

INTRODUCTION: Approximately 25%-30% of patients with non-small cell lung cancer (NSCLC) develop central nervous system (CNS) metastases during the course of the disease; this percentage is higher in patients with epidermal growth factor receptor (EGFR) mutations. Leptomeningeal metastases, infrequent in the advanced setting, have a particularly dismal prognosis. Osimertinib, a third-generation EGFR inhibitor, can provide effective and durable response in this setting. CASE DESCRIPTION: We present a 62-year-old man with progressive vomiting, headache, short-term memory impairment, and left lower limb hyposthenia. Computed tomography (CT) showed bilateral lung nodules, multiple lymphadenopathies, liver and bone metastases, and CNS and leptomeningeal dissemination, including multiple parenchymal nodules located at supra- and infratentorial brain. Bone needle biopsy documented TTF1+ lung adenocarcinoma. Whole brain radiotherapy (WBRT) and symptomatic treatments were started. Next-generation sequencing reported deletion of exon 19 of EGFR and mutation 8 of TP53. Osimertinib 80 mg was promptly started and WBRT interrupted. Some days after the patient experienced repetitive seizures and neurologic worsening, antiepileptic drugs and dexamethasone were implemented, with gradual improvement. Radiologic evaluation, including brain MRI and thorax-abdominal CT, showed partial response on CNS as well as extracranial sites, which was sustained. CONCLUSIONS: First-line treatment with osimertinib can be safe and effective in EGFR-mutated NSCLC even in presence of multiple negative predictive factors (poor Performance Status, diffuse leptomeningeal involvement, TP53 comutation), suggesting that deferring local treatments can be feasible in this setting, allowing the patient to maintain a good quality of life.

False positives and false negatives in neuroendocrine tumors diagnosis: clinical reports.

Differential diagnosis NETs may be highly challenging. In order to exclude conditions that may mimic a neuroendocrine neoplasms, a deep knowledge of all the aspects of the disease, together with an adequate capacity to interpret clinical data and imaging findings and to put them in right correlation, are strongly warranted. Patients which suspected neuroendocrine neoplasms should be referred to reference centers to receive optimal multidisciplinary care.

An unusually large pleural mesothelioma with an outstanding clinical response and long lasting survival: a case report and literature review.

Malignant pleural mesothelioma is a neoplasm characterized by an increasing incidence and poor prognosis. When surgical treatment cannot be performed, systemic chemotherapy remains the main therapeutic option. Here we report the case of a 41-year-old female patient with epithelioid malignant pleural mesothelioma who was treated with carboplatin and pemetrexed despite her critical condition. She showed an impressive response to this first-line chemotherapy and, after disease progression, to further chemotherapy with gemcitabine and vinorelbine. She is still alive, with unexpectedly long-lasting survival.

Recurrent thrombosis followed by Lazarus response in ROS1 rearranged NSCLC treated with crizotinib: a case report.

INTRODUCTION: Patients with cancer have higher risk of thrombosis compared to the general population and particularly lung adenocarcinoma is considered at high risk for venous thromboembolism. Some targetable oncogenic drivers are supposed to further increase this risk. CASE DESCRIPTION: A 35-year-old man who had developed a recurrent venous thromboembolism and pulmonary embolism (PE) was diagnosed with ROS1 rearranged non-small cell lung cancer (NSCLC). While molecular examinations were ongoing, he developed progressive respiratory failure. For PE and thrombosis worsening with detection of right heart thrombus, he underwent therapy with unfractionated heparin. Despite initial good radiologic results, only with the start of crizotinib did the patient's clinical condition significantly improve to configure a Lazarus response. CONCLUSIONS: Cancer diagnosis should always be considered in patients with unprovoked thrombosis and, if NSCLC is diagnosed, genetic alterations should be always sought after. A possible relation between venous thromboembolism and oncogenic drivers, particularly for ALK translocations, has been hypothesized. Similarly to ALK-positive NSCLC, ROS1 rearranged disease has been associated with an increased thromboembolic risk. Further studies are needed to better evaluate this relation and to evaluate the potential benefit of a prophylactic anticoagulating treatment in this subset of patients.

Systemic Treatment of Patients With Gastrointestinal Cancers During the COVID-19 Outbreak: COVID-19-adapted Recommendations of the National Cancer Institute of Milan.

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak poses a major challenge in the treatment decision-making of patients with cancer, who may be at higher risk of developing a severe and deadly SARS-CoV-2 infection compared with the general population. The health care emergency is forcing the reshaping of the daily assessment between risks and benefits expected from the administration of immune-suppressive and potentially toxic treatments. To guide our clinical decisions at the National Cancer Institute of Milan (Lombardy region, the epicenter of the outbreak in Italy), we formulated Coronavirus-adapted institutional recommendations for the systemic treatment of patients with gastrointestinal cancers. Here, we describe how our daily clinical practice has changed due to the pandemic outbreak, with the aim of providing useful suggestions for physicians that are facing the same challenges worldwide.

Single-institution series of early-stage Merkel cell carcinoma: long-term outcomes in 95 patients managed with surgery alone.

AIM: To determine the long-term outcomes of early-stage Merkel cell carcinoma (MCC) patients managed with surgery alone. METHODS: Ninety-five consecutive patients were reviewed. Patients were treated by wide local excision. Clinically negative regional nodes were either followed up (n=42) or staged with sentinel lymph node biopsy (n=21), and clinically positive nodes underwent lymph node dissection (n=32). RESULTS: Median follow-up was 65 months. A total of 45 (47%) patients relapsed, with 80% of the recurrences occurring within 2 years and 96% within 5 years. The 5-year crude cumulative incidence (CCI) of recurrence and disease-specific survival (DSS) were 52% and 67%, respectively. CCI of local 5-year recurrence was 5% for the study cohort. Patients with MCC in the head and neck region had a 5-year local-recurrence CCI of 19%, and patients with MCC in the extremity and trunk region had a 5-year local-recurrence CCI of 2% (P=0.007). Comparing patients with 2 metastatic lymph nodes, the 5-year regional-recurrence CCI was 0% versus 39% (P=0.004). The 5-year distant-recurrence CCI was higher in clinically node-positive patients compared with node-negative patients (37% versus 12%; P=0.005). Patients with MCC in the head and neck region experienced no distant recurrences, patients with MCC in the extremity and trunk region had a 5-year distant-recurrence CCI of 22%, and patients with occult primary had a 5-year distant-recurrence CCI of 49% (P=0.023). The 5-year DSS rate was 80% for pathologically node-negative patients. CONCLUSION: The prognosis for surgically managed early-stage MCC is variable. Thus multidisciplinary tumor-board consultation is needed to optimize individual patient management.

Pitfalls in the diagnosis of neuroendocrine tumors: atypical clinical and radiological findings as cause of medical mistakes.

AIMS AND BACKGROUND: Carcinoids are infrequent neoplasms arising from neuroendocrine cells. Due to blurred symptoms and the presence of equivocal diagnostic findings, these tumors are sometimes misdiagnosed. Therefore, increased rates of false neuroendocrine tumors represent an emerging problem in clinical practice. Our aim is to alert clinicians on this matter by supplying them with useful warnings. METHODS: In the specialized neuroendocrine tumor study Center Centro di Riferimento per lo Studio e la Cura dei Carcinoidi e dei Tumori Neuroendocrini (Ce.Ri.Ca), some patients highly suspected to have a neuroendocrine tumor have been recognized as having false neuroendocrine tumors. The related clinical and instrumental findings leading to a previous wrong neuroendocrine tumor diagnosis are reported. RESULTS: From July 2006 to December 2008, 88 consecutive cases of neuroendocrine tumors (Nets) were referred at Ce.Ri.Ca. In the former group, 8 cases of false Nets were discovered while in the remaining 80 cases a correct Net diagnosis was carried out. Watchful differential diagnoses and skill appraisal of laboratory investigations resulted in: chronic atrophic gastritis with enterochromaffin-like cell hyperplasia (4 cases), estrogen-deprivation syndrome (1), hypochondriac disorder (1), metabolic syndrome (1), and sarcoidosis (1). CONCLUSIONS: Neuroendocrine tumors are still relatively known clinical entities. To discriminate false neuroendocrine tumors from neuroendocrine tumors requires a good expertise and a large daily practice with the disease. Good knowledge and skillfulness in identifying biochemical alterations and false radiological positive results could avoid both patient inconvenience and very expensive workup. The importance of a multidisciplinary approach in specialized centers is emphasized.

Combination of Immunotherapy and Brain Radiotherapy in Metastatic Melanoma: A Retrospective Analysis.

BACKGROUND: Up to 40% of patients with metastatic melanoma (MM) develop brain metastases. Radiotherapy (RT) may potentiate the effects of immunotherapy (IO), even on distant sites (abscopal effect). MATERIAL AND METHODS: We retrospectively analyzed all our MM patients treated with IO within 6 months before/after brain RT between 2012 and 2016. Progression-free (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with those of controls treated with IO during the same period. RESULTS: Thirty-six cases and 25 controls were identified. Among cases, 23 patients received an anti-CTLA4 agent and 13 an anti-PD1 agent. Eighteen cases were treated with stereotactic RT and 18 with whole-brain RT. Median PFS from the beginning of RT was 4 months in first-line and 2 months in second-line treatment. A third of the cases progressed at first evaluation after RT. Median OS from the beginning of RT was 7 months in first-line and 4 months in second-line treatment. Median PFS and OS of each treatment line showed a trend towards inferiority compared with those of controls. CONCLUSION: Synergism between RT and IO was not observed in our case series. No cases of abscopal effect were seen, and most patients underwent early systemic progression after RT.

Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer.

OBJECTIVES: Alectinib demonstrated superior efficacy and a safety profile that compared favorably with crizotinib in treatment-naïve ALK+ non-small-cell lung cancer (NSCLC) in the phase III ALEX study. We present patient-reported outcomes (PROs) from ALEX to assess disease burden, treatment-related symptom tolerability, and health-related quality of life (HRQoL) with alectinib versus crizotinib. MATERIALS AND METHODS: Patients were randomized to receive alectinib 600 mg or crizotinib 250 mg twice daily until disease progression, death, or withdrawal. Pre-specified PRO endpoints were: mean change from baseline in symptoms, HRQoL, and functioning; and time to deterioration (TTD) in cough, dyspnea, chest pain, arm/shoulder pain, fatigue, and a composite of three symptoms (cough, dyspnea, chest pain). PRO data were collected using EORTC QLQ-C30 and LC13 questionnaires. Raw scores were standardized to a 0-100-point range, with a ≥10-point score change defined as clinically meaningful. TTD was defined as the time from randomization until confirmed clinically meaningful deterioration (i.e., a ≥10-point score change from baseline). RESULTS: Baseline completion rates and characteristics were balanced in the PRO-evaluable population (alectinib n = 100, 66%; crizotinib n = 97, 64%). On average, alectinib-treated patients reported clinically meaningful improvements in lung cancer symptoms for longer than crizotinib-treated patients. Between-treatment differences in lung cancer symptoms tended to favor alectinib from 11.1 months (45 weeks) onwards, around the time of median PFS with crizotinib (11.1 months). TTD in lung cancer symptoms was similar between treatment arms, despite longer duration of symptom improvement with alectinib; composite symptom endpoint (hazard ratio 1.10 [95% confidence interval: 0.72-1.68]). Duration of clinically meaningful improvement in HRQoL was longer with alectinib versus crizotinib (Week 88 vs. Week 68, respectively). Better patient-reported tolerability was observed with alectinib versus crizotinib on common treatment-related symptoms. CONCLUSION: PRO data support the superior efficacy and tolerability of alectinib relative to crizotinib demonstrated in the ALEX study.

Weighing the prognostic role of hyponatremia in hospitalized patients with metastatic solid tumors: the HYPNOSIS study.

Previous works linked low sodium concentration with mortality risk in cancer. We aimed at weighing the prognostic impact of hyponatremia in all consecutive patients with metastatic solid tumors admitted in a two-years period at our medical oncology department. Patients were included in two cohorts based on serum sodium concentration on admission. A total of 1025 patients were included, of whom 279 (27.2%) were found to be hyponatremic. The highest prevalence of hyponatremia was observed in biliary tract (51%), prostate (45%) and small-cell lung cancer (38.9%). With a median follow-up of 26.9 months, median OS was 2 months and 13.2 months for the hyponatremia versus control cohort, respectively (HR, 2.65; P < 0.001). In the multivariable model, hyponatremia was independently associated with poorer OS (HR, 1.66; P < 0.001). According to the multivariable model, a nomogram system was developed and validated in an external set of patients. We weighed over time the influence of hyponatremia on survival of patients with metastatic solid tumors and pointed out the possibility to exploit serum sodium assessment to design integrated prognostic tools. Our study also highlights the need for a deeper characterization of the biological role of extracellular sodium levels in tumor development and progression.

Oral maintenance metronomic vinorelbine versus best supportive care in advanced non-small-cell lung cancer after platinum-based chemotherapy: The MA.NI.LA. multicenter, randomized, controlled, phase II trial.

BACKGROUND: Oral vinorelbine administered at the maximum tolerated dose has already showed activity and a good safety profile in advanced non-small-cell lung cancer (NSCLC). The MA.NI.LA study was a phase II, multicenter, randomized, controlled trial that aimed to assess the effects of a 'switched maintenance' regimen with oral metronomic vinorelbine (OMV) in patients with NSCLC who had not progressed after first-line platinum-based chemotherapy. PATIENTS AND METHODS: Patients were randomly assigned in a 1:1 ratio to either OMV (50 mg three-times weekly) as maintenance treatment or best supportive care (BSC). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective disease control rate (DCR, CR + PR + SD), safety and quality of life. RESULTS: In total, 61 and 59 patients were assigned to OMV and BSC, respectively. At a median follow-up of 23.9 (IQR 10.2-38.2) months, patients treated with OMV reported a significantly lower progression rate compared to patient in the BSC arm (89% [54/61] vs 96% [56/58]; HR 0.73; 90% CI 0.53-0.999, p = 0.049). Median PFS for patients treated with vinorelbine was 4.3 months (95% CI 2.8-5.6) vs 2.8 months (95% CI 1.9-4.5) for patients receiving BSC. This benefit was specifically evident in patients aged ≥70 years, in current smokers, and in those who reported disease stabilization as best response to induction chemotherapy. OS and response rate and quality of life were similar in the two arms. Drop-out rate for major toxicity with OMV was unexpectedly high (25%, 14/61) mainly due to grade 3-4 neutropenia (11%, 7/61). Conclusions In patients with unselected NSCLC achieving disease control after platinum-based chemotherapy switch maintenance therapy with OMV prolonged PFS compared to BSC; however, the optimal dose of OMV requires further investigation.