Advances in breast cancer (BC) therapy are limited by the absence of well-established biomarkers for DNA-damage targeted treatments. We evaluated the predictive and prognostic value of homologous recombination repair (HRR) deficiency (HRD) by RAD51 nuclear foci and stromal tumour-infiltrating lymphocytes (TILs) in early-stage BC patients with suspected germline susceptibility. Among 291 patients, HRD by RAD51 was found in 78.4% of tumours, and 69.8% had low TILs (<30%). In 178 patients treated with neoadjuvant chemotherapy, pathologic complete response (pCR) was higher in those with HRD vs HRR-proficient (HRP) tumours (52.3% vs 36.4%); RAD51 remained independently associated with pCR (p = 0.03). Overall survival (OS) favoured HRD, with 5-year OS of 89.2% vs 82.8% in HRP (p = 0.009), with stronger evidence in triple-negative TILs-low disease (p = 0.005). These findings support RAD51-based HRD assessment as a predictive and prognostic biomarker that may guide treatment decisions in early-stage BC.
Background: Metastatic renal cell carcinoma (mRCC) has a dismal prognosis. Effective prognostic and predictive factors are needed. A higher haemoglobin (Hb) / red cell distribution width (RDW) ratio is known to be related to better outcomes. Here we evaluated the prognostic value of the Hb/RDW ratio in pre-treated mRCC patients receiving nivolumab. Material and methods: This is a sub-analysis of the retrospective Meet-URO 15 study, on pre-treated patients with mRCC, receiving nivolumab. The first objective was to investigate the prognostic role of Hb/RDW ratio, in terms of overall survival (OS) and progression-free survival (PFS). Results: 356 were included in the present analysis. Patients were mainly males with a median age of 63 years. We classified patients in high and low Hb/RDW ratio, according to two different cut-offs: 0.9frequently used in literature, and 0.7, result of the time-dependent AUC analysis.. Median OS and PFS were 22.3 months (95 %CI 19.4–29.0) and 5.6 months (95 %CI 4.74.–7.53), respectively. At univariable analysis, higher Hb/RDW ratio was related to longer OS (p < 0.001) and PFS (p = 0.011); the multivariable model confirmed only the association between a Hb/RDW ratio ≥ 0.7 and better OS. Conclusions: The Hb/RDW ratio is a manageable and practical prognostic tool in patients with cancer; its prognostic value for OS was confirmed in pre-treated mRCC patients, receiving nivolumab, only using a cut-off value derived from a time-dependent AUC.
568 Background: Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, most patients do not achieve benefits, emphasizing the need to understand the mechanisms of resistance. Previous analysis highlighted the association between blood cholesterol levels, passive cholesterol diffusion efflux and oncological outcomes. Here we reported the preliminary data of the CHOMET study, aimed at assessing the cholesterol transporters ABCA1 and ABCG1 expression in ICIs-treated patients with metastatic renal cell carcinoma (mRCC). Methods: The present is a monocentric retrospective study on patients with mRCC receiving first-line ICI-based combination. The primary objective was to assess the ABCA1/G1 expression by immunohistochemistry and its impact on overall survival (OS). The secondary objectives included the impact on progression-free survival (PFS) and disease control rate (DCR: complete and partial responses plus stable disease). Survival times were calculated by Kaplan-Meier method and comparisons between groups were performed by log-rank test. Results: 61 patients were enrolled, clear cell RCC was the most frequent histotype (78.8%). With a median follow-up of 30.4 months (22.1-37.0), median OS was 38.9 months (CI 33.9-NR) and median PFS was 24.4 months (CI 10.1-34.2). For the present analysis, the ABCA1/G1 histological evaluation of tumour samples was available for 43 and 41 patients, respectively. The median expression level was 50% for ABCA1 and 45% for ABCG1. We found a significant correlation between higher ABCA1/G1 staining intensity expression and both shorter median OS and PFS (Table). Similarly they were inversely related to DCR (Table). Conclusions: For the first time, we reported a high expression of ABCA1/G1 cholesterol transporter on kidney cancer. An inverse association between staining intensity expression and oncological outcomes in patients receiving ICIs combinations was found. Oncological outcomes according to ABCA1/G1 staining intensity expression. IHC mPFS months (95%CI) mOSmonths (95%CI) DCR% ABCA1 intensity expression 1+ 30.1 (25.8-NR) NR (NR-NR) 88.9 2+ 24.4 (9.9-NR) NR (33.9-NR) 72.7 3+ 4.5 (3.20-NR) 12.2 (8.2-NR) 25.0 p value 0.016 < 0.001 0.013 ABCG1 intensity expression 1+ 62.7 (25.6-NR) NR (NR-NR) 87.5 2+ 17.4 (9.9-NR) NR (NR-NR) 68.2 3+ 6.65 (2.9-NR) 12.2 (3.8-NR) 37.5 p value 0.006 0.013 0.101 DCR: disease control rate, IHC: immunohistochemistry, mOS: median overall survival, mPFS: median progression-free survival, NR: not reached.
Background/objectives: Cancer patients are more vulnerable to SARS-CoV-2 infection and COVID-19 due to their immunocompromised status. This study aims to evaluate the risk of SARS-CoV-2 infection, as well as COVID-19 prevalence and mortality, in cancer patients during the first wave of the COVID-19 pandemic in a virus epicenter of Northern Italy. Methods: This retrospective analysis included 40,148 prevalent cancer patients from the province of Parma, Italy, between February and June 2020. Patients were identified from health system records and classified by cancer subtype, treatment status, and COVID-19 diagnosis. The risk of infection and mortality was analyzed using odds ratios (OR) and hazard ratios (HR). Results: Among cancer patients, those on active cancer treatment had a higher cumulative risk of all-cause death (HR 1.83, p < 0.000268). Cancer subtype significantly impacted COVID-19 outcomes, with breast cancer patients showing lower incidence and mortality compared to those with lung, colorectal, or bladder cancers. Conclusions: Cancer patients, especially those on active treatment, are at increased risk of COVID-19 infection and death. Tailored prevention strategies, including prioritization of vaccination and careful management of cancer treatments, are crucial to mitigate risks during pandemics. These findings provide valuable insights for clinical decision-making in oncological care during public health crises.
Background:immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic urothelial carcinoma (mUC), significantly improving survival outcomes. However, a subset of patients do not respond to ICIs, prompting research into potential predictive factors. Commonly prescribed medications such as corticosteroids, proton-pump inhibitors (PPIs), antibiotics (Abs), antihypertensives, and analgesics may influence ICI effectiveness. Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC, treated with ICIs. We selected the most relevant studies and performed a narrative review. Results:corticosteroids, PPIs and Abs have been associated with reduced survival in ICI-treated patients, including those with mUC. In contrast, antihypertensive agents like renin-angiotensin system inhibitors and beta-blockers may enhance ICI efficacy, though evidence remains inconclusive. The impact of other medications, such as statins, metformin, and analgesics, on ICI outcomes is less clear, with some data suggesting a detrimental impact on immune response. Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.
Objectives Patients with lung cancer experience high rates of hospitalisation, mainly due to the high risk of complications that emerge during the natural history of the disease. We designed a retrospective, single-centre, observational study aimed at defining the clinical predictors of 30-day mortality in hospitalised patients with lung cancer.Methods Clinical records from the first admission of patients with lung cancer to the oncology ward of the University Hospital of Parma from 1 January 2017 to 1 January 2022 were collected.Results 251 consecutive patients were enrolled at the time of data cut-off. In the univariate analysis, baseline clinical predictors of 30-day mortality were Eastern Cooperative Oncology Group performance status (ECOG PS) (=2 vs 0-1: 27.5% vs 14.8%, p=0.028), high Blaylock Risk Assessment Screening Score (BRASS) (high vs intermediate-low: 34.3% vs 11.9%, p<0.001), presence of pain (yes vs no: 24.4% vs 11.7%, p=0.009), number of metastatic sites (=3 vs <3: 26.5% vs 13.4%, p=0.017) and presence of bone metastases (yes vs no: 29.0% vs 10.8%, p=0.001). In the multivariate analysis, high BRASS remained significantly associated with increased 30-day mortality (high vs intermediate-low; OR 2.87, 95% CI 1.21 to 6.78, p=0.016).Conclusion Our results suggest that baseline poor ECOG PS, high BRASS, presence of pain, high tumour burden and presence of bone metastases could be used as clinical predictors of 30-day mortality in hospitalised patients with lung cancer. In particular, the BRASS scale should be used as a simple tool to predict 30-day mortality in hospitalised patients with lung cancer.
Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC). Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context. Results: High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, ρ = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, ρ = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors. Conclusions: In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations.
Background Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs). Methods We planned a prospective observational study (PROVIDENCE) to assess serum vitamin D levels in patients with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion on survival and toxicity outcomes. In an exploratory analysis, we compared the clinical outcomes of cohort 1 with a control cohort of patients followed at the participating centers who did not receive systematic vitamin D repletion. Results Overall, 164 patients were prospectively recruited in the PROVIDENCE study. In cohort 1, consisting of 101 patients with 94.1% hypovitaminosis (≤ 30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 patients assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no patients having adequate levels (> 30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of patients at the three months re-assessment. Compared to a retrospective control group of 238 patients without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer overall survival (OS, p = 0.013), time to treatment failure (TTF, p = 0.017), and higher disease control rate (DCR, p = 0.016 ). The Inverse Probability of Treatment Weighing (IPTW) fitted multivariable Cox regression confirmed the significantly decreased risk of death (HR 0.55, 95%CI: 0.34–0.90) and treatment discontinuation (HR 0.61, 95%CI: 0.40–0.91) for patients from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade immune-related adverse events (irAEs) was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, patients from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03–0.85). Conclusion The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcomes of patients with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs.
Lung cancer patients experience high rates of hospitalization, mainly due to the high risk of complications that emerge during the natural history of disease. We designed a retrospective single-center observational study aimed at defining clinical predictors of 30-day mortality in hospitalized lung cancer patients. Clinical records from the first admission of lung cancer patients to the Oncology ward of University Hospital of Parma from January 1st, 2017, to January 1st, 2022, were collected. 251 patients were consecutively enrolled. Median age was 66 years (Range, 29-85). 161 (64.1%) patients were men and 217 (86.5%) current/former smokers. ECOG PS was 0-1 in 182 (72.5%) cases. The most frequent histology was adenocarcinoma (n=120, 47.8%), followed by small-cell carcinoma (n=73, 29.0%), and the majority of patients had stage IV disease (n=209, 83.3%). Main reasons for hospital admission were anticancer treatment start (n=146, 58.2%) and cancer-related complications (n=75, 29.9%). The most frequently symptoms at admission were pain (n=131, 52.2%) and dyspnea (n=92, 36.7%). Median Blaylock Risk Assessment Screening Score (BRASS) was 7 (Range, 1-28). Clinical deterioration (n=102, 40.6%) was the main complication during the hospital stay. Baseline clinical predictors of 30-day mortality were poor ECOG PS (≥ 2 vs 0-1: 27.5% vs 14.8%, p=0.028), high BRASS (High vs Intermediate-Low: 34.3% vs 11.9%, p<0.001), high number of metastatic sites (≥ 3 vs < 3: 26.5% vs 13.4%, p=0.017), presence of bone metastases (Yes vs No: 29.0% vs 10.8%, p=0.001) and presence of pain (Yes vs No: 24.4% vs 11.7%, p=0.009). At multivariate analysis, only high BRASS remained significantly associated with higher 30-day mortality (BRASS High vs Intermediate-Low Odds Ratio 2.87, 95% CI 1.21-6.78, p=0.016). Baseline poor ECOG PS, high BRASS, high tumour burden, presence bone metastases and pain were associated with increased 30-day mortality in hospitalized lung cancer patients, with high BRASS being statistically significant at multivariate analysis. Our study draw attention on BRASS as a new feasible potential indicator of 30-day mortality in hospitalized lung cancer patients.
OBJECTIVE:To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).METHODS:A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups.RESULTS:Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association (p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype (p = 0.05).CONCLUSION:PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.
BACKGROUND Burnout is a stress-induced occupational related syndrome, characterized by Emotional Exhaustion (EE), feeling of depersonalization (DP) and low sense of professional accomplishment (PA). The aim of this study is to analyse the effectiveness of interventions in decreasing health professionals Burnout as well as work and life-style risk factors. Methods: A survey in Medical Oncology Department in the University Hospital of Parma was conducted using the validated Maslach Burnout Inventory (MBI) and two additional questionnaires exploring lifestyle and work factors. An 8-months intervention involved fortnight meetings by facilitators, incorporated elements of reflection, shared experiences and managing emotions. Six months after the end of the intervention a second survey was performed among the participants using MBI and the same questionnaires mentioned above. Results: EE resulted the most problematic score in Day Hospital: after the 8-month intervention we described a significant decreasing in EE score especially for Day Hospital operators (from 16.7 to 10.9) and a considerable reduction in DP score. In the Oncology Ward a correlation between lack of collaboration among different health categories and DE score was detected; in the Day Hospital the absence of solid working teams was related to higher EE scores. Conclusion: The Oncology professional health care personnel are at the greatest risk of Burnout. Our study in Oncology Department shows that specific intervention should be used to prevent and reduce Burnout. Effective personal health care strategies should be incorporated into routine oncology care to prevent and treat Burnout.
Objective: To identify histopathological and immunophenotypical features with potential predictive or prognostic value in patients undergoing pulmonary metastasectomy from renal cell carcinoma (RCC). Methods: We retrospectively collected all consecutive patients undergoing pulmonary metastasectomy from RCC after prior nephrectomy. Paired samples of primary tumors and corresponding pulmonary metastases were analyzed, revising histopathological features and testing C-MET, mTOR, and PD-L1 by immunohistochemistry. Results: A total of 25 patients were included. Median overall survival (mOS) from metastasectomy was 5.5 years (95% CI = 1.9–9.1). The laterality of metastases had a significant predictive value, with median relapse-free survival (mRFS) from metastasectomy not reached (NR) at mean follow-up (FU) of 60.8 months for left lung involvement, mRFS of 52.9 months (95% CI = 0–145.5) for the right lung and 6.4 months (95% CI = 1.7–11) for bilateral metastases ( p = 0.028). Primary RCC with positive expression of mTOR had higher mOS after metastasectomy than negative cases ( p < 0.001), NR at mean FU of 4.3 years versus mOS of 2 years (95% CI = 0.7–3.3), respectively. PD-L1 positivity on intra-tumor (TILs) and peri-tumor (RILs) infiltrating lymphocytes of metastases was related to higher OS, NR versus 2 years (95% CI = 1.2–2.7, p = 0.003), and NR versus 1.4 years (95% CI = 0.2–2.6, p = 0.012), respectively. The shorter was the surgical interval, the more probably the metastases had high c-MET expression (>70%) ( p = 0.007) and PD-L1 expression >10% on TILs ( p = 0.024). Conclusions: mTOR positivity on primary RCC could be a favorable prognostic factor to select patients for pulmonary metastasectomy. The positive impact of PD-L1 expression on immune cells is opposite to the well-known negative prognostic value of PD-L1 on tumor cells in RCC.
Triple-negative breast cancer (TNBC) that do not achieve pathological complete response (pCR) have unfavorable prognosis. The RAD51 score is a functional assay able to identify Homologous Recombination Repair (HRR)-deficient tumors. In this setting, it may add prognostic value and guide post-neoadjuvant treatments.
Patients (pts) with cancer are purported to be more vulnerable to coronavirus disease 2019 (COVID-19). However, cancer encompasses a spectrum of heterogenous tumor subtypes. The aim of this study was to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and COVID-19 prevalence according to tumor subtype in the resident cancer population of the Province of Parma (Emilia Romagna Region, Nothern Italy) during the first wave of COVID-19 pandemic in Italy. We analyzed data from the Parma Province Cancer Registry, COVID-19 hospital medical records, and local surveillance system of all laboratory-confirmed cases tested positive for SARS-CoV-2 from the beginning of the outbreak (February, 20) to July 19, 2020. All the Parma resident cancer population was classified as either "active" or "inactive" according to the evidence of any referral to health services, for any reason, during the observation period. Study analyses were adjusted for patient demographics, tumor subtype and period of cancer diagnosis. 40,148 cancer pts (mean age 68; 57.8% females; 45.1% active) were analyzed. The cumulative risk of SARS-CoV-2 infection was 11.2% for cancer pts vs. 7% for non-cancer subjects (P < 0.0001). The overall COVID-19 attack rate was 2.2% (95% CI, 2.0-2.4) and 2.6% (95% CI, 2.4-2.9) for inactive and active cancer pts, respectively. The cumulative incidence of COVID-19 was higher in active vs. inactive cancer subjects (HR 1.18, P = 0.01). In the active cancer group, the cumulative incidence of COVID-19 was higher in lung cancer pts vs. other tumors (HR 4.3). In the same group, HR for breast cancer pts was 0.86. Interestingly, the subgroup analysis of COVID-19 cumulative incidence showed a significant interaction between active patient status and hematological malignancies. In our study, cancer pts were more susceptible to SARS-CoV-2 infection. The cumulative incidence of COVID-19 was higher in active vs. inactive cancer subjects. However, cancer is a heterogeneous group of diseases and pts with different tumor types had differing susceptibility to COVID-19 phenotypes. COVID-19 fatality rates for subgroups will be reported at the meeting.
Introduction: Upfront criteria to foresee immune checkpoint inhibitors (ICIs) efficacy are far from being identified. Thus, we integrated blood descriptors of pro-inflammatory/immunosuppressive or effective anti-tumor response to non-invasively define predictive immune profiles in ICI-treated advanced non-small cell lung cancer (NSCLC). Methods: Peripheral blood (PB) was prospectively collected at baseline from 109 consecutive NSCLC patients undergoing ICIs as first or more line treatment. Soluble PD-L1 (sPD-L1) (immunoassay), CD8 + PD-1 + and NK (FACS) cells were assessed and interlaced to generate an Immune effector Score (I eff S). Lung Immune Prognostic Index (LIPI) was computed by LDH levels and derived Neutrophil-to-Lymphocyte Ratio (dNLR). All these parameters were correlated with survival outcome and treatment response. Results: High sPD-L1 and low CD8 + PD-1 + and NK number had negative impact on PFS (P < 0.001), OS (P < 0.01) and ICI-response (P < 0.05). Thus, sPD-L1(high), CD8 + PD-1 + (low )and NKlow were considered as risk factors encompassing I eff S, whose prognostic power outperformed that of individual features and slightly exceeded that of LIPI. Accordingly, the absence of these risk factors portrayed a favorable IeffS characterizing patients with significantly (P < 0.001) prolonged PFS (median NR vs 2.3 months) and OS (median NR vs 4.1) and greater benefit from ICIs (P < 0.01). We then combined each risk parameter composing IeffS and LIPI (LDHhigh, dNLR(high)), thus defining three distinct prognostic classes. A remarkable impact of IeffS-LIPI integration was documented on survival outcome (PFS, HR = 4.61; 95%CI = 2.32-9.18; P < 0.001; OS, HR= 4.03; 95%CI=1.91-8.67; P < 0.001) and ICI-response (AUC =0.90, 95%CI= 0.81-0.97, P < 0.001). Conclusion: Composite risk models based on blood parameters featuring the tumor-host interaction might provide accurate prognostic scores able to predict ICI benefit in NSCLC patients.
OBJECTIVES:In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of "druggable" mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients.MATERIALS AND METHODS:We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019. The primary endpoint of the study was represented by overall survival (OS), defined as the time from CT initiation to death. Secondary outcome endpoints of the SCAI (progression free survival, PFS, objective response rate, ORR and toxicity) and explorative biomarkers (lactate dehydrogenase, LDH, and neutrophil-to-lymphocyte ratio, NLR during immunotherapy) were also analyzed.RESULTS:In our study population of 342 NSCLC patients, SCAI obtained a median OS of 6.8 months (95 % confidence interval, CI 5.5-8.1), median PFS of 4.1 months (95 % CI 3.4-4.8) and ORR of 22.8 %. A "Post-CKI score" was constructed by combining significant predictors of OS at the multivariate analyses (sex, ECOG PS, disease control with prior immunotherapy), Harrell'C was 0.65, (95 % CI:0.59-0.71).CONCLUSIONS:Despite the late-line settings, our findings support the hypothesis that previous immunotherapy might increase the sensitivity of the tumor to the subsequent chemotherapy. The "Post-CKI score" was clinically effective in successfully discriminating three distinct prognostic subgroups of patients after the failure of CKI, representing a possibly useful tool for the tailored decision-making process of advanced treatment-line settings in NSCLC.