Prognostic Factors across Poorly Differentiated Neuroendocrine Neoplasms: A Pooled Analysis.

INTRODUCTION: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggressive clinical course and poor prognosis. No reliable prognostic markers have been validated to date; thus, the definition of a specific NEC prognostic algorithm represents a clinical need. This study aimed to analyze a large NEC case series to validate the specific prognostic factors identified in previous studies on gastro-entero-pancreatic and lung NECs and to assess if further prognostic parameters can be isolated. METHODS: A pooled analysis of four NEC retrospective studies was performed to evaluate the prognostic role of Ki-67 cut-off, the overall survival (OS) according to primary cancer site, and further prognostic parameters using multivariable Cox proportional hazards model and machine learning random survival forest (RSF). RESULTS: 422 NECs were analyzed. The most represented tumor site was the colorectum (n = 156, 37%), followed by the lungs (n = 111, 26%), gastroesophageal site (n = 83, 20%; 66 gastric, 79%) and pancreas (n = 42, 10%). The Ki-67 index was the most relevant predictor, followed by morphology (pure or mixed/combined NECs), stage, and site. The predicted RSF response for survival at 1, 2, or 3 years showed decreasing survival with increasing Ki-67, pure NEC morphology, stage III-IV, and colorectal NEC disease. Patients with Ki-67 <55% and mixed/combined morphology had better survival than those with pure morphology. Morphology pure or mixed/combined became irrelevant in NEC survival when Ki-67 was ≥55%. The prognosis of metastatic patients who did not receive any treatment tended to be worse compared to that of the treated group. The prognostic impact of Rb1 immunolabeling appears to be limited when multiple risk factors are simultaneously assessed. CONCLUSION: The most effective parameters to predict OS for NEC patients could be Ki-67, pure or mixed/combined morphology, stage, and site.

Ki-67 Index of 55% Distinguishes Two Groups of Bronchopulmonary Pure and Composite Large Cell Neuroendocrine Carcinomas with Distinct Prognosis.

BACKGROUND: Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical, and molecular approach could be used for their prognostic evaluation. METHODS: Morphological (including combined features), proliferative (mitotic count/Ki-67 index), immunohistochemical (napsin A, p40, TTF-1, CD44, OTP, SSTR2A, SSTR5, mASH1, p53, RB1, and MDM2), and genomic (TP53, RB1, ATM, JAK2, KRAS, and STK11) findings were analyzed in BP-LCNECs from 5 Italian centers, and correlated with overall survival (OS). The Ki-67 index was expressed as the percentage of positive cells in hot spots as indicated in the WHO 2019 Digestive System Tumors and, for Co-LCNECs, the Ki-67 index was evaluated only in the LCNEC component. RESULTS: A total of 111 LCNECs were distinguished into 70 pure LCNECs, 35 Co-LCNECs (27 with adenocarcinoma [ADC] and 8 with squamous cell carcinoma [SqCC]), and 6 LCNECs with only napsin A immunoreactivity. The Ki-67 index cutoff at 55% evaluated in the neuroendocrine component was the most powerful predictor of OS (log-rank p = 0.0001) in all LCNECs; 34 cases had a Ki-67 index <55% (LCNEC-A) and 77 had a Ki-67 index ≥55% (LCNEC-B). Statistically significant differences in OS (log-rank p = 0.0001) were also observed between pure and Co-LCNECs. A significant difference in OS was found between pure LCNECs-A and Co-LCNECs-A (p < 0.05) but not between pure LCNECs-B and Co-LCNECs-B. Co-LCNEC-ADC and LCNEC napsin A+ cases had longer OS than pure LCNEC and Co-LCNEC-SqCC cases (log-rank p = 0.0001). On multivariable analysis, tumor location, pure versus combined features, and napsin A, but no single gene mutation, were significantly associated with OS after adjustment for Ki-67 index and study center (p < 0.05). CONCLUSIONS: The Ki-67 proliferation index and the morphological characterization of combined features in LCNECs seem to be important tools for predicting clinical outcome in BP-LCNECs.

CT texture analysis for prediction of EGFR mutational status and ALK rearrangement in patients with non-small cell lung cancer.

PURPOSE: To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutated, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinomas and distinguish them from wild-type tumors on pre-treatment CT scans. MATERIALS AND METHODS: Texture analysis was performed using proprietary software TexRAD (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT scans of 84 patients with metastatic primary lung adenocarcinoma. Textural features were quantified using the filtration-histogram approach with different spatial scale filters on a single 5-mm-thick central slice considered representative of the whole tumor. In order to deal with class imbalance regarding mutational status percentages in our population, the dataset was optimized using the synthetic minority over-sampling technique (SMOTE) and correlations with textural features were investigated using a generalized boosted regression model (GBM) with a nested cross-validation approach (performance averaged over 1000 resampling episodes). RESULTS: ALK rearrangements, EGFR mutations and wild-type tumors were observed in 19, 28 and 37 patients, respectively, in the original dataset. The balanced dataset was composed of 171 observations. Among the 29 original texture variables, 17 were employed for model building. Skewness on unfiltered images and on fine texture was the most important features. EGFR-mutated tumors showed the highest skewness while ALK-rearranged tumors had the lowest values with wild-type tumors showing intermediate values. The average accuracy of the model calculated on the independent nested validation set was 81.76% (95% CI 81.45-82.06). CONCLUSION: Texture analysis, in particular skewness values, could be promising for noninvasive characterization of lung adenocarcinoma with respect to EGFR and ALK mutations.

Efficacy of nivolumab in pre-treated non-small-cell lung cancer patients harbouring KRAS mutations.

BACKGROUND: The present study investigated the efficacy and safety of nivolumab in pre-treated patients with advanced NSCLC harbouring KRAS mutations. METHODS: Clinical data and KRAS mutational status were analysed in patients treated with nivolumab within the Italian Expanded Access Program. Objective response rate, progression-free survival and overall survival were evaluated. Patients were monitored for adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS: Among 530 patients evaluated for KRAS mutations, 206 (39%) were positive while 324 (61%) were KRAS wild-type mutations. KRAS status did not influence nivolumab efficacy in terms of ORR (20% vs 17%, P = 0.39) and DCR (47% vs 41%, P = 0.23). The median PFS and OS were 4 vs 3 months (P = 0.5) and 11.2 vs 10 months (P = 0.8) in the KRAS-positive vs the KRAS-negative group. The 3-months PFS rate was significantly higher in the KRAS-positive group as compared to the KRAS-negative group (53% vs 42%, P = 0.01). The percentage of any grade and grade 3-4 AEs were 45% vs 33% (P = 0.003) and 11% vs 6% (P = 0.03) in KRAS-positive and KRAS-negative groups, respectively. CONCLUSIONS: Nivolumab is an effective and safe treatment option for patients with previously treated, advanced non-squamous NSCLC regardless of KRAS mutations.

Texture features of colorectal liver metastases on pretreatment contrast-enhanced CT may predict response and prognosis in patients treated with bevacizumab-containing chemotherapy: a pilot study including comparison with standard chemotherapy.

PURPOSE: Bevacizumab added to chemotherapy can improve survival in patients with metastatic colorectal cancer, but no predictive factors of efficacy are available in clinical practice. The aim of this study is to assess the predictive and prognostic value of texture analysis on pretreatment contrast-enhanced CT in patients affected by colorectal liver metastases. MATERIALS AND METHODS: Forty-three patients with colorectal liver metastases were retrospectively included in the study: 23 treated with bevacizumab-containing chemotherapy (group A), and 20 with standard chemotherapy (group B). Target liver lesions were analyzed by texture analysis of pretreatment contrast-enhanced CT. Texture analysis produced the parameter uniformity, describing lesion heterogeneity. Radiological response was classified after 3 months according to RECIST-1.1. Overall survival (OS) and progression-free survival (PFS) were considered to be outcome indicators. Multivariable logistic regression and survival analysis were performed. RESULTS: Uniformity was lower in responders than in nonresponders (p < 0.001) in group A but not in group B. Lesion CT density was lower in nonresponders in both groups (p = 0.03 and 0.02, respectively). In group A, uniformity was independently correlated with radiological response (odds ratio = 20, p = 0.01), OS and PFS (relative risks 6.94 and 5.05, respectively; p = 0.005 and p = 0.004, respectively). In group B, no variables were correlated with radiological response, OS or PFS. CONCLUSION: Texture analysis on contrast-enhanced CT stratified response probability and prognosis in patients with colorectal liver metastases treated with bevacizumab-containing therapy. This result was specific for the bevacizumab group.

Eribulin in Heavily Pretreated Metastatic Breast Cancer Patients in the Real World: A Retrospective Study.

OBJECTIVES: The aim of this study was to investigate efficacy and safety of eribulin in heavily pretreated patients with advanced breast cancer (BC) in a real-life setting. METHODS: This retrospective monocentric study included patients with HER-2-negative metastatic BC, pretreated with anthracyclines and taxanes, who were referred to the Oncology Department of Spedali Civili of Brescia from May 2012 to April 2017. Patients received the same dose of eribulin as that used in the EMBRACE trial: 1.4 mg/m2 on days 1 and 8 every 21 days. RESULTS: In a total of 53 patients, 32% obtained a partial response, 11% a stable disease, and 43% a clinical benefit (CB). After a median follow-up of 36 months, median progression-free survival (PFS) was 4.7 months and median overall survival (OS) 13.53 months. Median PFS was significantly longer in patients who reported a CB compared to those with no CB, while survival outcomes (PFS and OS) were better in patients who received > 6 cycles of eribulin. Eribulin showed a good tolerability profile with acceptable toxicities, similar to those reported in EMBRACE. CONCLUSIONS: Our experience in a real-world setting confirms the activity, efficacy, and good tolerability profile of eribulin in heavily pretreated BC patients.

Hepatoprotective effect of N-acetylcysteine in trabectedin-induced liver toxicity in patients with advanced soft tissue sarcoma.

PURPOSE: Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity. METHODS: Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment. The study aim was to retrospectively explore trabectedin administration in terms of number of cycles, mean dose, and dose intensity (DI) in patients who received NAC as compared with those who did not. Secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS: A total number of 18 patients were enrolled in this study. Nine received NAC and nine did not. The median number of administered trabectedin cycles, mean trabectedin dose/cycles, and median DI was comparable in the two groups (p = 0.450, p = 0.534, and p = 0.450, respectively). The PFS and OS curves overlapped. CONCLUSION: This explorative study suggests that NAC can have a hepatoprotective activity in patients receiving trabectedin allowing to maintain an adequate dose intensity and continuative administration in patients with impaired liver and renal function or developing treatment-induced hepatotoxicity. A prospective randomized trial is warranted.

Amiloride Is Effective in the Management of Abiraterone-Induced Mineralocorticoid Excess Syndrome without Interfering with Its Antineoplastic Activity.

BACKGROUND: The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES). METHODS: The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC). Then, using the in vitro experimental model of PCa cell lines, the possible effects of drugs usually used in the clinical management of CRPC patients on PCa cell viability were investigated. RESULTS: Amiloride/HCT led to a complete disappearance of all clinical and biochemical signs of abiraterone-induced MCES in the 5 treated patients. The in vitro study showed that abiraterone treatment significantly decreased cell viability of both androgen receptor (AR)-expressing VCaP (vertebral-cancer of the prostate) and LNCaP (lymph node carcinoma of the prostate) cells, with no effect on AR-negative PC-3 cells. Prednisolone, spironolactone, and eplerenone increased LNCaP cell viability, while amiloride reduced it. The non-steroid aldosterone antagonist PF-03882845 did not modify PCa cell viability. CONCLUSIONS: The combination of amiloride/HCT was effective in the management of abiraterone-induced MCES. Amiloride did not negatively interfere with the abiraterone inhibition of PCa cell viability in vitro.

Echocardiographic evaluation in subjects with α1-Antitrypsin deficiency.

BACKGROUND: α1-Antitrypsin (AAT) deficiency (AATD) is a genetic condition associated with early-onset panacinar emphysema and, less often, vascular disease. Recently, abnormal elastic properties of ascending aortic wall were described in ZZ genotype AATD subjects who incidentally showed an increased left ventricular mass. MATERIALS AND METHODS: To evaluate biventricular dimensions, valvular apparatus, systolic and diastolic function, 33 AATD subjects with ZZ genotype and 33 healthy subjects matched for age and sex underwent a complete echocardiographic assessment. RESULTS: Compared to controls, AATD subjects showed increased left ventricular mass (160 ± 59 g vs. 121 ± 70 g, P < 0.001), a higher incidence of left and right ventricular diastolic dysfunction (30% vs. 16%, P < 0.001 and 45% vs. 20%, P < 0.001, respectively) and mitral valve prolapse (35% vs. 6%, P < 0.001). In contrast, there was no difference between the two groups in diameters and systolic function of both ventricles and in the ejection fraction of left ventricle. The functions of aortic and tricuspidal valves were also similar. CONCLUSIONS: In the presence of greater left ventricular mass, a significantly higher incidence of left and right ventricular diastolic dysfunction and mitral valve prolapse occurs in AATD subjects (ZZ genotype). These findings strongly suggest an abnormal remodelling process in cardiac tissue in AATD.

Positron Emission Tomography/Computed Tomography for the Pleural Staging of Malignant Pleural Mesothelioma: How Accurate Is It?

BACKGROUND: Careful clinical staging in patients with malignant pleural mesothelioma (MPM) is fundamental in management planning. Positron emission tomography/computed tomography (PET/CT) is increasingly recognized as an important staging modality. OBJECTIVES: The purpose of this study was to assess whether the metabolic activity of the pleural tumor detected with PET/CT correlates with specific endoscopic features and pleural distribution of the lesions as assessed by medical thoracoscopy. METHODS: Consecutive patients with MPM and available PET/CT performed before thoracoscopy were separated into 2 groups, according to their standardized uptake value (SUV). Kaplan-Meier-analysis for survival was performed on groups with low and high SUV. Agreement between PET/CT and thoracoscopy evaluation was analyzed using Cohen's kappa coefficient. The Wilcoxon test was used to compare the median SUV, and the χ(2) test was used to evaluate differences in endoscopic findings. RESULTS: A total of 32 patients were included. The median maximum SUV (SUV max) was 6.1 and patients were separated into 2 groups based on this cutoff. Patients with SUV max <6.1 had a better survival than those with SUV max ≥6.1 (p = 0.005). The comparison between PET/CT and thoracoscopy showed a fair agreement for visceral and diaphragmatic pleural involvement and moderate agreement for the presence of nodular lesions. There was a statistically significant association between median SUV max and visceral pleural involvement; nodular lesions and visceral pleural involvement were more common in the high-SUV group than in the low-SUV group (p = 0.0012 and p = 0.03, respectively). CONCLUSIONS: PET/CT data may be predictive of thoracoscopic features of MPM associated with prognosis and staging, but the correlation is moderate at best. A degree of disagreement exists between these two modalities, which supports thoracoscopy as the gold standard for assessment of local invasion in MPM.

Positive FDG-PET/CT of the pleura twenty years after talc pleurodesis: three cases of benign talcoma.

The FDG-PET (fluorine-18 fluorodeoxyglucose positron emission tomography) scan is used with increasing frequency to investigate pleural abnormalities and to determine the possibility of neoplastic invasion. However, false-positive findings are not uncommon and talc pleurodesis has been reported to cause hypermetabolic pleural thickenings up to 5 years after the procedure. We report the cases of 3 patients (2 of whom had a history of asbestos exposure) requiring talc pleurodesis for recurrent pneumothoraces between 1988 and 1990, who were investigated in 2011 for pleural abnormalities. Avid pleural thickening on FDG-PET scan mimicking pleural cancer was found, but this was deemed secondary to the pleurodesis. Talc pleurodesis generates inflammation which promotes pleural adhesions. This inflammatory reaction could decrease with time, as in other inflammatory processes. Since talc is not metabolized by the body, the FDG-PET scan can remain positive, most likely because of a foreign-body granulomatous reaction, even 20 years later. It is important to be aware of this possibility and to question patients with pleural abnormalities about past procedures and mention such procedures to the colleagues who are responsible for interpreting metabolic imaging. Follow-up of hypermetabolic pleural lesions attributed to talc pleurodesis is important for the detection of new pleural lesions or neoplastic evolution.

Diagnosis of Pleural Mesothelioma: Is Everything Solved at the Present Time?

Ranked high in worldwide growing health issues, pleural diseases affect approximately one million people globally per year and are often correlated with a poor prognosis. Among these pleural diseases, malignant pleural mesothelioma (PM), a neoplastic disease mainly due to asbestos exposure, still remains a diagnostic challenge. Timely diagnosis is imperative to define the most suitable therapeutic approach for the patient, but the choice of diagnostic modalities depends on operator experience and local facilities while bearing in mind the yield of each diagnostic procedure. Since the analysis of pleural fluid cytology is not sufficient in differentiating historical features in PM, histopathological and morphological features obtained via tissue biopsies are fundamental. The quality of biopsy samples is crucial and often requires highly qualified expertise. Since adequate tissue biopsy is essential, medical or video-assisted thoracoscopy (MT or VATS) is proposed as the most suitable approach, with the former being a physician-led procedure. Indeed, MT is the diagnostic gold standard for malignant pleural pathologies. Moreover, this medical or surgical approach can allow diagnostic and therapeutic procedures: it provides the possibility of video-assisted biopsies, the drainage of high volumes of pleural fluid and the administration of sterile calibrated talcum powder under visual control in order to achieve pleurodesis, placement of indwelling pleural catheters if required and in a near future potential intrapleural therapy. In this context, dedicated diagnostic pathways remain a crucial need, especially to quickly and properly diagnose PM. Lastly, the interdisciplinary approach and multidisciplinary collaboration should always be implemented in order to direct the patient to the best customised diagnostic and therapeutic pathway. At the present time, the diagnosis of PM remains an unsolved problem despite MDT (multidisciplinary team) meetings, mainly because of the lack of standardised diagnostic work-up. This review aims to provide an overview of diagnostic procedures in order to propose a clear strategy.

The importance of integrated therapies on cancer: Silibinin, an old and new molecule.

In the landscape of cancer treatments, the efficacy of coadjuvant molecules remains a focus of attention for clinical research with the aim of reducing toxicity and achieving better outcomes. Most of the pathogenetic processes causing tumour development, neoplastic progression, ageing, and increased toxicity involve inflammation. Inflammatory mechanisms can progress through a variety of molecular patterns. As is well known, the ageing process is determined by pathological pathways very similar and often parallel to those that cause cancer development. Among these complex mechanisms, inflammation is currently much studied and is often referred to in the geriatric field as 'inflammaging'. In this context, treatments active in the management of inflammatory mechanisms could play a role as adjuvants to standard therapies. Among these emerging molecules, Silibinin has demonstrated its anti-inflammatory properties in different neoplastic types, also in combination with chemotherapeutic agents. Moreover, this molecule could represent a breakthrough in the management of age-related processes. Thus, Silibinin could be a valuable adjuvant to reduce drug-related toxicity and increase therapeutic potential. For this reason, the main aim of this review is to collect and analyse data presented in the literature on the use of Silibinin, to better understand the mechanisms of the functioning of this molecule and its possible therapeutic role.

Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program.

BACKGROUND: Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRASp.G12C-mutated advanced non-small-cell lung cancer (NSCLC) within the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP). METHODS: Sotorasib (960 mg, orally, once daily) was available on physician request for KRASp.G12C mutant advanced NSCLC patients. Clinical-pathological and molecular data were collected from the Italian ATLAS real-world registry. Patients underwent CT-scan and responses were evaluated by RECIST criteria. Efficacy and tolerability outcomes have been assessed. RESULTS: A total of 196 advanced NSCLC patients were treated across 30 Italian centers. Median age was 69 years old (range 33-86). Most patients were male (61 %), former (49 %) or current smokers (43 %), with ECOG-PS 0/1 (84 %) and adenocarcinoma subtype (90 %). 45 % and 32 % of patients received sotorasib in 2nd and 3rd line, respectively. Overall, response rate was 26 % and the median duration of response was 5.7 months (95 % CI: 4.4-7.0). Median PFS and OS were 5.8 months (95 % CI: 5 - 6.5) and 8.2 months (95 % CI: 6.3 - 9.9). Grade 3-4 TRAEs occurred in 16.5 % of patients, with Grade ≥ 3 liver enzyme increase and TRAEs-related discontinuation reported in 12 % and 4.6 % of cases. CONCLUSION: Real-world data from the Italian EAP confirm the tolerability and effectiveness of sotorasib in patients with KRASp.G12C-mutated advanced NSCLC and highlight the value of the national ATLAS network as source of real-world evidence driving the clinical management of NSCLC patients.

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.

Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy.

OBJECTIVES: To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). METHODS: Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. RESULTS: Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. CONCLUSIONS: TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy.

SCLC Treatment in the Immuno-Oncology Era: Current Evidence and Unmet Needs.

Small cell lung cancer (SCLC) represents about 13%-15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results. However, despite the high tumor mutational load and the chronic pro-inflammatory state induced by prolonged exposure to cigarette smoke, the benefit observed with immunotherapy is very modest and most patients experience disease recurrence. Unfortunately, biological, clinical, or molecular factors that can predict this risk have not yet been identified. Thanks to these clinically meaningful steps forward, SCLC is no longer considered an "orphan" disease. Innovative treatment strategies and combinations are currently under investigation to further improve the expected prognosis of patients with SCLC. Following the recent therapeutic innovations, we have reviewed the available literature data about SCLC management, with a focus on current unmet needs and potential predictive factors. In detail, the role of radiotherapy; fragile populations, such as elderly or low-performance status patients (ECOG PS 2), usually excluded from randomized studies; predictive factors of response useful to optimize and guide therapeutic choices; and new molecular targets and future combinations have been explored and revised.

Coronavirus Disease 2019 Outcomes, Patient Vaccination Status, and Cancer-Related Delays During the Omicron Wave: A Brief Report From the TERAVOLT Analysis.

Introduction: The Thoracic Centers International coronavirus disease 2019 (COVID-19) Collaboration (TERAVOLT) registry found approximately 30% mortality in patients with thoracic malignancies during the initial COVID-19 surges. Data from South Africa suggested a decrease in severity and mortality with the Omicron wave. Our objective was to assess mortality of patients with thoracic malignancies with the Omicron-predominant wave and evaluate efficacy of vaccination. Methods: A prospective, multicenter observational study was conducted. A total of 28 institutions contributed data from January 14, 2022, to February 4, 2022. Inclusion criteria were any thoracic cancer and a COVID-19 diagnosis on or after November 1, 2021. End points included mortality, hospitalization, symptomatic COVID-19 infection, asymptomatic COVID-19 infection, and delay in cancer therapy. Analysis was done through contingency tables and a multivariable logistic model. Results: We enrolled a total of 346 patients. Median age was 65 years, 52.3% were female, 74.2% were current or former smokers, 86% had NSCLC, 72% had stage IV at time of COVID-19 diagnosis, and 66% were receiving cancer therapy. Variant was unknown for 70%; for those known, Omicron represented 82%. Overall mortality was 3.2%. Using multivariate analysis, COVID-19 vaccination with booster compared with no vaccination had a protective effect on hospitalization or death (OR = 0.30, confidence interval: 0.15-0.57, p = 0.0003), whereas vaccination without booster did not (OR = 0.64, confidence interval: 0.33-1.24, p = 0.1864). Cancer care was delayed in 56.4% of the patients. Conclusions: TERAVOLT found reduced patient mortality with the most recent COVID-19 surge. COVID-19 vaccination with booster improved outcomes of hospitalization or death. Delays in cancer therapy remain an issue, which has the potential to worsen cancer-related mortality.