Assessing the role of colonic and other anatomical sites uptake by [18 F]FDG-PET/CT and immune-inflammatory peripheral blood indexes in patients with advanced non-small cell lung cancer treated with first-line immune checkpoint inhibitors.

BACKGROUND: Inflammation in non-small cell lung cancer (NSCLC) may impair the response to immune checkpoint inhibitors (ICIs) and can be indicated by peripheral blood inflammatory indexes. 2-deoxy-2-[18 F]fluoro-D-glucose positron emission tomography/computed tomography ([18 F] FDG-PET/CT) may be used as a marker of inflammation by measuring glucose metabolism in different colonic sites. METHODS: This retrospective analysis aimed to investigate the correlation between [18 F] FDGPET/CT SUVratio in six gastrointestinal districts, the spleen, the pharynx and the larynx alongside the most avid tumor lesion with peripheral blood inflammatory indexes, including the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammatory index (SII, i.e., NLR times platelets) and lactate dehydrogenase (LDH), in patients with [18 F] FDG-PET/CT staged IV NSCLC who received first-line immune checkpoint inhibitors (ICIs). The role of SUVratios and peripheral blood inflammatory indexes in predicting overall survival (OS) and progression-free survival (PFS) was then explored. RESULTS: A total of 43 patients were treated with first-line ICI alone (58%) or in combination with chemotherapy (42%). A significant correlation was only found between the rectosigmoid SUVratio and NLR (p = 0.0465). NLR >5.5 and LDH > 333.5 were associated with a worse OS (p = 0.033 and p = 0.009, respectively). The SII was associated with a worse PFS in patients treated with ICI alone (p = 0.033). None of the SUVratios were significantly associated with OS or PFS, although a high left colon SUVratio showed a trend toward a worse PFS. CONCLUSION: There was no significant correlation between [18 F]FDG PET/CT uptake in different anatomical sites, and in the tumor, and systemic immune-inflammatory indexes. The prognostic role of high left colon SUVratio deserves further investigation.

Therapeutic efficacy of platinum/etoposide regimens in the treatment of advanced poorly differentiated neuroendocrine carcinomas of the lung: A retrospective analysis.

Background: Lung neuroendocrine neoplasms (NENs) are rare malignancies developed from bronchial mucosa. Because of its rarity and complex histopathology, there is limited data on the role of chemotherapy in this subset of tumors. Few studies regarding the treatment of poorly differentiated lung NENs, known as neuroendocrine carcinomas (NECs), are available and many limits are detectable as heterogeneity of tumor samples including different origins and different clinical behaviors, moreover, no evidence of therapeutic advances have been achieved along the last thirty years. Method: We performed a retrospective analysis of 70 patients affected by poorly differentiated lung NECs: half of patients underwent a first line therapy with a combination of cisplatin plus etoposide; the remaining patients receiving carboplatin instead of cisplatin, plus etoposide. Results: In our analysis, the outcomes of patients treated with either cisplatin or carboplatin schedule are similar in terms of ORR (44% versus 33%), DCR (75% versus 70%), PFS (6.0 versus 5.0 months) and OS (13.0 versus 10 months). Median number of chemotherapy cycles was 4 (range 1-8). The 18% of patients required a dose reduction. Main toxicities reported were hematological (70.5%), gastrointestinal (26.5%) and fatigue (18%). Conclusion: Survival rate in our study suggests that high grade lung NENs are characterized by an aggressive behavior and a poor prognosis, despite the treatment with platinum/etoposide according to available data. Clinical results of present study contribute to strengthen available data on the usefulness of platinum/etoposide regimen in the treatment of poorly differentiated lung NENs.

First-line immunotherapy in non-small cell lung cancer: how to select and where to go.

INTRODUCTION: Immunotherapy (IO) has established a new milestone in lung cancer treatment. Several registrational studies have approved immune checkpoint inhibitors (ICIs) in different settings, including the metastatic nonsmall cell lung cancer (NSCLC). As well known, responders are just a certain proportion of patients; therefore, their selection by using predictive factors has stood out as a crucial issue to address in tailoring a patient-centered care. AREAS COVERED: In our review we propose a detailed yet handy cross section on ICIs as first-line treatment in metastatic NSCLC, regarding indications, histological, clinical, and blood-based biomarkers, other than their mechanisms of resistance and new immunological actionable targets. We performed a literature search through PubMed entering keywords complying with crucial features of immunotherapy. EXPERT OPINION: IO represents the backbone of lung cancer treatment. Trials are currently testing novel immune blockade agents assessing combinatorial approaches with standard ICIs, or antibody drug conjugates (ADC), harboring immunological targets. Perfecting patients' selection is an ongoing challenge and a more and more urgent need in order to best predict responders who will consistently benefit from it.

Efficacy outcomes and prognostic factors from real-world patients with advanced non-small-cell lung cancer treated with first-line chemoimmunotherapy: The Spinnaker retrospective study.

BACKGROUND: Efficacy outcomes and prognostic factors of real-world patients with advanced non-small cell lung cancer (aNSCLC) treated with first-line chemoimmunotherapy are still limited. PATIENTS AND METHODS: In the retrospective Spinnaker study, data was collected from patients in six United Kingdom and one Swiss oncology centres with first-line pembrolizumab plus platinum-based chemotherapy. Efficacy outcomes and potential prognostic factors were estimated aiming at developing a prognostic model. RESULTS: Three-hundred-eight patients were included, 32% ≥ 70 years, with ≥ 3 metastatic sites in 33%, brain or liver metastases in 10% and 12%, respectively. With a median follow-up of 18.0 months (mo.) (range, 15.9-20.1), median overall survival (OS) and progression-free survival (PFS) were 12.7 mo. (range, 10.2-15.2), and 8.0 mo. (range, 7.1-8.8), respectively. The neutrophils-to-lymphocytes ratio (NLR) and systemic immune-inflammatory index (SII) (i.e., NLR × platelet count) were both significantly higher in ECOG PS 1 (p = 0.0147 and p = 0.0018, respectively), underweight or normal body mass index (p = 0.0456 and p = 0.0062, respectively), ≥3 metastatic sites (p = 0.0069 and p = 0.112), pretreatment steroids (p = 0.0019 and p = 0.0017). By MVA, the number of metastatic sites ≥ 3 (p < 0.001 and p = 0.002), squamous histology (p = 0.033 and p = 0.013) and SII ≥ 1444 (p = 0.031 and p = 0.009, respectively) were associated with both worse OS and PFS and led to a highly discriminating three-class risk prognostic model. CONCLUSION: Real-world PFS with chemoimmunotherapy in aNSCLC patients is similar to that reported in clinical trials. A high number of metastatic sites, squamous histology and high SII are adverse prognostic factors that might contribute to a clinically useful prognostic model.

International Survey on Frailty Assessment in Patients with Cancer.

BACKGROUND: Frailty negatively affects the outcomes of patients with cancer, and its assessment might vary widely in the real world. The objective of this study was to explore awareness and use of frailty screening tools among the ONCOassist healthcare professionals (HCPs) users. MATERIALS AND METHODS: We sent 2 emails with a cross-sectional 15-item survey in a 3-week interval between April and May 2021. Differences in the awareness and use of tools according to respondents' continents, country income, and job types were investigated. RESULTS: Seven hundred thirty-seven HCPs from 91 countries (81% physicians, 13% nurses, and 5% other HCPs) completed the survey. Three hundred and eighty-five (52%) reported assessing all or the majority of their patients; 518 (70%) at baseline and before starting a new treatment. Three hundred and four (43%) HCPs were aware of performance status (PS) scores only, 309 (42%) age/frailty/comorbidity (AFC) screening, and 102 (14%) chemotoxicity predictive tools. Five hundred and thirty-seven (73%) reported using tools; 423 (57%) just PS, 237 (32%) AFC, and 60 (8%) chemotoxicity ones. Reasons for tools non-use (485 responders) were awareness (70%), time constraints (28%), and uselessness (2%). There were significant differences in awareness and use of screening tools among different continents, country income, job types, and medical specialties (P < .001 for all comparisons). CONCLUSION: Among selected oncology HCPs, there is still a worldwide lack of knowledge and usage of frailty screening tools, which may differ according to their geography, country income, and education. Targeted initiatives to raise awareness and education are needed to implement frailty assessment in managing patients with cancer.

Risk of SARS-CoV2-Related Mortality in Non-Small Cell Lung Cancer Patients Treated with First-Line Immunotherapy Alone or in Combination with Chemotherapy.

BACKGROUND: The impact of systemic anticancer treatments on SARS-CoV-2-related mortality is still debatable. METHODS: By a retrospective analysis of patients with non-small-cell lung cancer (NSCLC) treated with first-line Pembrolizumab or in combination with chemotherapy (ChT) during the first surge of the pandemic. RESULTS: The adjusted risk of death was higher in patients treated with ChT + Pembrolizumab (HR 4.6, 1.2-17.4, p = 0.02). The SARS-CoV-2-related mortality rate was higher in patients treated with ChT + Pembrolizumab (p = 0.03), ≥70 years (p = 0.03) and current smokers (p = 0.17). CONCLUSIONS: The addition of ChT to immunotherapy could be associated with increased risk of mortality and higher SARS-CoV-2-related mortality rate.

Role of the Combination of Cyclin-Dependent Kinase Inhibitors (CDKI) and Radiotherapy (RT) in the Treatment of Metastatic Breast Cancer (MBC): Advantages and Risks in Clinical Practice.

Targeting cell cycle has become the gold standard for metastatic breast cancer (MBC), being cyclin-dependent kinase inhibitors (CDKIs) cornerstones of its treatment, alongside radiotherapy (RT). To date, no definite evidence regarding safety and efficacy of the combination of CDKIs plus radiotherapy (RT) is currently available. Purpose of this review is to collect data in favor or against the feasibility of the association of CDKIs + RT, describing its potential adverse events. Our review shows how CDKI + RT allows an overall satisfying disease control, proving to be effective and causing a grade of toxicity mainly influenced by the site of irradiation, leaning to favourable outcomes for sites as liver, spine or brain and to poorer outcomes for thoracic lesions or sites close to viscera; controversial evidence is instead for bone treatment. Toxicity also varies from patient to patient. To sum up, our contribution enriches and enlightens a still indefinite field regarding the feasibility of CDKIs + RT, giving cues for innovative clinical management of hormone-responsive MBC.

Three-Dimensional Deep Noninvasive Radiomics for the Prediction of Disease Control in Patients With Metastatic Urothelial Carcinoma treated With Immunotherapy.

INTRODUCTION: Immunotherapy is effective in a small percentage of patients with cancer and no reliable predictive biomarkers are currently available. Artificial Intelligence algorithms may automatically quantify radiologic characteristics associated with disease response to medical treatments. METHODS: We investigated an innovative approach based on a 3-dimensional (3D) deep radiomics pipeline to classify visual features of chest-abdomen computed tomography (CT) scans with the aim of distinguishing disease control from progressive disease to immune checkpoint inhibitors (ICIs). Forty-two consecutive patients with metastatic urothelial cancer had progressed on first-line platinum-based chemotherapy and had baseline CT scans at immunotherapy initiation. The 3D-pipeline included self-learned visual features and a deep self-attention mechanism. According to the outcome to the ICIs, a 3D deep classifier semiautomatically categorized the most discriminative region of interest on the CT scans. RESULTS: With a median follow-up of 13.3 months (95% CI, 11.1-15.6), the median overall survival was 8.5 months (95% CI, 3.1-13.8). According to disease response to immunotherapy, the median overall survival was 3.6 months (95% CI, 2.0-5.2) for patients with progressive disease; it was not yet reached for those with disease control. The predictive accuracy of the 3D-pipeline was 82.5% (sensitivity 96%; specificity, 60%). The addition of baseline clinical factors increased the accuracy to 92.5% by improving specificity to 87%; the accuracy of other architectures ranged from 72.5% to 90%. CONCLUSION: Artificial Intelligence by 3D deep radiomics is a potential noninvasive biomarker for the prediction of disease control to ICIs in metastatic urothelial cancer and deserves validation in larger series.

Efficacy of Pembrolizumab Monotherapy in Patients With or Without Brain Metastases From Advanced Non-Small Cell Lung Cancer With a PD-L1 Expression ≥50%.

The authors conducted a multicenter retrospective study on the outcome of programmed death-ligand 1 tumor proportion score≥50% advanced non-small cell lung cancer patients treated with first-line pembrolizumab according to the presence/absence of brain metastases. A total of 282 patients were included, of whom 56 had brain metastases that were treated with upfront local radiation therapy in 80.3% of cases. The overall response rate was 39.2% and 44.4% in patients with and without brain metastases (P=0.48), respectively, while intracranial response rate and intracranial disease control rate were 67.5% and 85.0%, respectively. The median time-to-treatment failure (TTF) and overall survival (OS) were 4.2 and 9.9 months versus 10.8 and 26.5 months for patients with and without brain metastases (P=0.06 and 0.05, respectively). Drug discontinuation rate due to treatment-related adverse events was 10.7% and 10.2% in patients with and without brain metastases, respectively. Multivariate analysis showed that baseline steroids was an independent predictor for a worse OS (P<0.001), while performance status (PS)≥2 was an independent predictor for a poorer TTF (P<0.001) and OS (P<0.001). In patients with brain metastases, only PS ≥2 was predicted for a worse TTF (P=0.02) and OS (P=0.03). Pembrolizumab has activity against brain metastases from non-small cell lung cancers with programmed death-ligand 1≥50%. Presence of brain metastases per se does not appear to be prognostic, and PS ≥2 seems to be the only factor associated with a worse outcome in patients with brain metastases.

Neutrophil-to-lymphocyte ratio in combination with PD-L1 or lactate dehydrogenase as biomarkers for high PD-L1 non-small cell lung cancer treated with first-line pembrolizumab.

The identification of prognostic and predictive biomarkers for high-programmed cell death-ligand 1 (PD-L1) advanced non-small cell lung cancer (aNSCLC) treated with first-line pembrolizumab could support the decision-making about possible combination therapies. To explore the baseline neutrophil-to-lymphocyte ratio (NLR) with the possible addition of PD-L1 tumour proportion score (TPS) level or lactate dehydrogenase (LDH) as possible prognostic biomarkers by a multicenter retrospective exploratory analysis aiming at identifying favourable-risk patients. Baseline NLR was available for all 132 high PD-L1 aNSCLC patients, PD-L1 level and LDH for 81 (61%) and 85 (64%) patients, respectively. NLR, PD-L1 and LDH cut-offs by receiver operating characteristic (ROC) curves were 4.9, 77.5% and 268.5, respectively. Seventy-one patients (54%) had NLR <5; 25 out of 81 NLR <5 (31%) had PD-L1 >80%, 26 out of 85 (31%) NLR <5 and normal LDH (nLDH). Median follow-up was 16.3 months. As compared to NLR >5, significantly better 2-year overall survival (OS) and progression-free survival (PFS) were observed with NLR <5 [62% vs. 41%, P=0.005, hazard ratio (HR) 0.45, and median of 12.0 vs. 5.7 months, P=0.01, HR 0.56, respectively], NLR <5 + PD-L1 >80% (81%, P=0.006, HR 0.20 and median of 14.7, P=0.03, HR 0.44, respectively), and NLR <5 + nLDH (74%, P=0.009, HR 0.25 and median of 14.7, P=0.02, HR 0.40, respectively). NLR <5 and NLR <5 + nLDH significantly associated with PD (P=0.008 and P=0.025, respectively) but not response rate (RR) (P=0.09 and P=0.07, respectively); NLR <5 + PD-L1 >80% both RR (P=0.03) and PD (P=0.02). NLR <5 ± PD-L1 >80% or nLDH could represent easy-to-assess tools to identify high PD-L1 aNSCLC patients with favourable outcome following first-line pembrolizumab monotherapy.

Are anti-PD1 and anti-PD-L1 alike? The non-small-cell lung cancer paradigm.

Anti-PD1 and anti-PD-L1 agents may have intrinsic and clinically relevant differences in the treatment of non-small cell lung cancer (NSCLC) patients. By reviewing currently available indirect evidence on these agents for NSCLC treatment, highlighting possible inter- and intra-class dissimilarities, anti-PD1 agents showed a higher response rate and a better outcome when combined with chemotherapy for the first-line treatment of patients with squamous and PD-L1 low advanced NSCLC, as compared to anti-PD-L1 agents. Conversely, anti-PD-L1 agents were responsible for less severe adverse events (AEs), particularly, immunerelated AEs. These differences could be explained by their different specific properties. Considering possible differences between anti-PD1 and anti-PD-L1 agents could be clinically relevant for treatment tailoring and inspiring new investigational approaches.