Bellmunt risk score as a survival predictor in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: The prognosis of metastatic castration-resistant prostate cancer (mCRPC) is influenced by numerous individual factors. Despite various proposed prognostic models, the clinical application of these remains limited, probably due to complexity. Our study aimed to evaluate the predictive value of the Bellmunt risk score, which is well-known for urothelial carcinoma and easily assessed, in mCRPC patients. METHODS: The Bellmunt risk score was calculated from three risk factors (Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥1, serum hemoglobin <10 g/dL, presence of liver metastases) in 125 patients who received first-line mCRPC treatment between 2005 and 2023. In addition, a modified score was established (one point each for hemoglobin <10 g/dL and the presence of liver metastases added to the ECOG PS). Associations with overall survival (OS) under first- and second-line therapy were tested using Cox regression analyzes, log-rank tests, concordance index (C-index) and time-dependent receiver operating characteristic. RESULTS: There is a significant correlation between the level of the Bellmunt risk score and shorter OS (hazard ratio: 3.23, 95% confidence interval: 2.06-5.05; log-rank p < 0.001; C-index: 0.724). The semi-quantitative modified risk score showed even better prognostic discrimination (log-rank p < 0.001, C-index: 0.764). The score and its dynamics were also predictive in the second-line setting (log-rank p < 0.001 and = 0.01; C-index: 0.742 and 0.595). CONCLUSIONS: The Bellmunt risk score is easy to assess and provides useful prognostic information in mCRPC, and can support physicians in their treatment decisions.

A novel prognostic model based on pretreatment serum albumin and ECOG PS for primary CNS lymphoma: an international, multi-center study.

BACKGROUND: Serum albumin has been demonstrated as prognostic parameter in non-Hodgkin lymphoma (NHL). Primary central nervous system lymphoma (PCNSL) is a rare extranodal NHL with highly aggressive behavior. In this study, we aimed at creating a novel prognostic model for PCNSL based on serum albumin levels. METHODS: We compared several commonly used laboratory nutritional parameters for predicting the survival of PCNSL patients using overall survival (OS) for outcome analysis and receiver operating characteristic curve analysis to determine the optimal cut-off values. Parameters associated with OS were evaluated by univariate and multivariate analyses. Independent prognostic parameters for OS were selected for risk stratification, including albumin ≤ 4.1 g/dL, ECOG PS > 1, and LLR > 166.8, which were associated with shorter OS; albumin > 4.1 g/dL, ECOG PS 0-1 and LLR ≤ 166.8, which were associated with longer OS, and five-fold cross-validation was used for evaluating predictive accuracy of identified prognostic model. RESULTS: By univariate analysis, age, ECOG PS, MSKCC score, Lactate dehydrogenase-to-lymphocyte ratio (LLR), total protein, albumin, hemoglobin, and albumin to globulin ratio (AGR) resulted statistically associated with the OS of PCNSL. By multivariate analysis, albumin ≤ 4.1 g/dL, ECOG PS > 1, and LLR > 166.8 were confirmed to be significant predictors of inferior OS. We explored several PCNSL prognostic models based on albumin, ECOG PS and LLR with 1 point assigned to each parameter. Eventually, a novel and effective PCNSL prognostic model based on albumin and ECOG PS successfully classified patients into three risk groups with 5-year survival rates of 47.5%, 36.9%, and 11.9%, respectively. CONCLUSIONS: The novel two-factor prognostic model based on albumin and ECOG PS we propose represents a simple but significant prognostic tool for assessing newly diagnosed patients with PCNSL.

Site of distant metastasis affects the prognosis with recurrent/metastatic head and neck squamous cell carcinoma patients treated with Nivolumab.

BACKGROUND: Nivolumab is approved for the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the influence of the site of distant metastasis on the efficacy of immune checkpoint inhibitor in R/M HNSCC remains unclear. We investigated the prognosis of R/M HNSCC patients treated with nivolumab, focusing on the site of distant metastasis. METHODS: We reviewed the data of R/M HNSCC patients treated with nivolumab between April 2017 and June 2020 at Saitama Prefectural Cancer Center. The differences in the prognosis were evaluated according to the site of distant metastasis. RESULTS: Of the 41 patients enrolled, 26 (63.4%) had lung metastasis, 7 (17.1%) had bone metastasis, and 4 (9.8%) had liver metastasis. Ten patients (24.4%) had single-organ distant metastasis (lung metastasis in all cases). Univariate analysis identified lung metastasis alone (single-organ distant metastasis) was associated with a significantly better prognosis [HR0.37 (95% CI) 0.14-0.97 p = 0.04], while liver metastasis was associated with a significantly worse prognosis [HR3.86 (95% CI) 1.26-11.8 p = 0.02]. Multivariate analysis identified lung metastasis alone and liver metastasis as independent prognostic factors. While 7 patients (70%) with lung metastasis alone could be continued on nivolumab treatment or received subsequent chemotherapy, only 1 patient (25%) with liver metastasis received subsequent chemotherapy. CONCLUSION: The site of distant metastasis affects the prognosis of R/M HNSCC patients treated with nivolumab. Lung metastasis alone appears to be associated with a better prognosis, in that it allows easier transition to subsequent chemotherapy, while liver metastasis associates with a worse prognosis.

Development and evaluation of a proxy for baseline ECOG PS in advanced non-small cell lung cancer, bladder cancer, and melanoma: An electronic health record study.

PURPOSE: Eastern Cooperative Oncology Group performance status (ECOG PS) is an important predictor for receipt of treatment and overall survival (OS) but is often unreported in routine care. We developed a proxy for baseline ECOG PS using electronic health records (EHRs). METHODS: We analyzed patients who were diagnosed with advanced non-small cell lung cancer (aNSCLC), advanced bladder cancer (aBCa), and advanced melanoma (aMEL) between 2011 and 2018 and had a baseline (reported between diagnosis and treatment) ECOG PS in a real-world database. We used stepwise multivariable logistic regression to model associations between baseline ECOG PS good (<2) versus poor (≥2) and sociodemographic, clinical, and laboratory measures in each cancer type. Predictive accuracy of classifying ECOG PS was assessed. We tested the association between OS and observed and predicted ECOG PS. RESULTS: In total, 20 697 aNSCLC patients, 2627 aBCa patients, and 2558 aMEL patients constituted the study population. Percentage of patients with poor ECOG PS ranged from 15.3% (aMEL) to 28.5% (aNSCLC). Poor ECOG PS was associated with more comorbid conditions, older age, lower body mass index, metastases, and abnormal laboratory indicators. Overall prediction accuracy using a 0.50 cutpoint was 73.3% for NSCLC, 73.8% for aBCa, and 85.4% for aMEL. The association of OS with ECOG PS was consistent between the observed and proxy measures. CONCLUSIONS: In the EHR-derived data, clinical, sociodemographic, and laboratory information were used to assign ECOG PS and enhance the use of real-world data in outcome studies.

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study).

OBJECTIVE: Azacitidine (Vidaza® ) is the standard treatment for patients with higher-risk myelodysplastic syndromes (MDS) not eligible for allogeneic stem cell transplantation. In the noninterventional study PIAZA, we evaluated the effectiveness and safety of azacitidine treatment in 149 patients with higher-risk MDS, chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) in routine clinical practice. METHOD: Patients were treated according to physician's discretion. Besides evaluation of safety and effectiveness, impact of covariates on progression-free survival (PFS) was assessed. RESULTS: Median age of patients was 75 years. 61.1% of patients were diagnosed with MDS, 31.5% with AML and 7.4% with CMML. Patients were treated with azacitidine for a median of seven cycles. Median PFS was 10.9 months. Median OS was 14.1 months. Two-year survival rate was 28.9%. 45.9% of patients showed CR or PR. Stable and progressive disease were observed in 37.2% and 8% of patients, respectively. Transfusion independence was reported in 64 of 89 patients. Eastern cooperative oncology group (ECOG) performance status (PS) and red blood cell (RBC) transfusion before azacitidine therapy were identified as predictive factors for PFS. CONCLUSION: In conclusion, we estimated the duration of PFS in a real-world setting and identified ECOG PS and RBC transfusion as predictive factors for PFS. The safety of azacitidine showed a similar profile as demonstrated in the pivotal clinical trials.

Multidisciplinary decision-making regarding chemotherapy for lung cancer patients-An age-based comparison.

Optimising decision-making in elderly patients is becoming increasingly urgent. We analysed treatment decisions and course of therapy for patients with lung cancer in different age categories: <65, 65-75, and 75 years and older. About 349 patients with lung cancer (median age 67.8 years), discussed at the multidisciplinary team meeting in the Diakonessenhuis Utrecht, the Netherlands, were reviewed. Multidisciplinary decision-making and subsequent clinical course were extracted from medical files. We found that 39% of eligible patients older than 75 years of age started treatment with chemotherapy compared to 80% of the younger patients (<65 and 65-75). When patients did receive chemotherapy, primary and secondary treatment adaptations were effectuated in 58%: for patients aged <65 in 49%, for patients aged 65-75 and >75 years in 66%. For 44% of all patients treated with chemotherapy, unplanned hospital admissions were required: in 42% for the patients <65, in 52% for those aged 65-75 and in 27% for >75 years. The decision-making process and course of treatment for lung cancer vary per age category. In particular, patients between 65 and 75 years of age might be more frail than initially thought. Age and frailty are important characteristics that need more attention.

Prognosis of patients with advanced hepatocellular carcinoma who failed first-line systemic therapy.

BACKGROUND & AIMS: No approved therapy is available for patients with advanced hepatocellular carcinoma (HCC) who fail first-line therapy. The prognosis of these patients, especially those eligible for clinical trials of second-line therapy, is unclear. METHODS: All patients who participated in clinical trials of first-line systemic therapy for metastatic or locally advanced HCC in a referral center of Taiwan between 2005 and 2011 were included. Their clinicopathologic characteristics, when the first-line treatment failed, were analyzed and correlated with the overall survival (OS) from the date of first-line treatment failure. RESULTS: A total of 192 patients were included. Before the start of the first-line therapy, all patients had Child-Pugh class A liver reserves and Cancer of the Liver Italian Program (CLIP) scores ≤4. After the failure of the first-line therapy, the median OS of the entire group was 4.0 months. Patients with Child-Pugh class A liver reserves, when the first-line treatment failed, had significantly better OS than patients with Child-Pugh class B or C liver reserves (median, A vs. B vs. C=7.5 vs. 1.3 vs. 1.0 month, p<0.001). According to the key eligibility criteria of 3 published clinical trials for second-line therapy, 41%-56% of patients were potentially eligible. Compared to patients who were ineligible for clinical trials, potentially eligible patients had longer OS with a median of 7.8-8.6 months. CONCLUSIONS: Patients with advanced HCC who failed first-line therapy could have substantially improved prognosis if they had Child-Pugh A liver reserves or were potentially eligible for clinical trials.

Induction chemotherapy backbone in frail patients with advanced NSCLC treated with chemotherapy plus pembrolizumab: a single institution retrospective audit of dose intensities from modified regimens.

Guidelines historically recommended mono-chemotherapy for the 1st line treatment of elderly patients with non-small cell lung cancer (NSCLC) and poor performance status (PS). Nowadays, there is no clear indication whether chemo-immunotherapy (chemo-IO) combinations can be effectively delivered in this population. We collected induction chemotherapy data in consecutive patients with advanced NSCLC treated with carboplatin-based chemotherapy regimens plus pembrolizumab, to compute the received dose intensity (RDI) from standard regimens or patient-tailored regimens modified due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous and squamous NSCLC, treated with carboplatin-pemetrexed or carboplatin-paclitaxel doublets plus pembrolizumab, respectively. The majority of patients were aged ≥ 70 years (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an Eastern Cooperative Oncology Group (ECOG) - PS of 0, 1 and 2, respectively. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori modified regimens due to poor PS, age, or comorbidities. Among patients with non-squamous NSCLC, median received doses of carboplatin and pemetrexed were 1.37 AUC/week and 138.8 mg/m2/week, with RDIs of 86% and 75% (p < 0.01) for patients treated with standard or modified regimens, respectively. Of note, the RDI was 57.9% among patients with ECOG-PS 2. However, patients treated with modified regimens experienced similar toxicities as those treated with standard regimens, despite being older (p < 0.01), with higher PS (p < 0.01) and more comorbid (p = 0.03). Patients treated with modified regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among patients with squamous NSCLC, 90% received modified regimens upfront, with median received doses of carboplatin and paclitaxel of 1.19 AUC/week and 40 mg/m2/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemotherapy plus pembrolizumab in frail patients, the RDI seems to be subtherapeutic, especially in those with squamous histology. Dedicated trials are needed to implement combination strategies in this population.

Clinical Characteristics and Outcomes of AIDS-Related Burkitt Lymphoma in China: A Retrospective Single-Center Study.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) - related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy (P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [HR] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 (HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Pomalidomide, Bortezomib, and Dexamethasone in Lenalidomide-Pretreated Multiple Myeloma: A Subanalysis of OPTIMISMM by Frailty and Bortezomib Dose Adjustment.

INTRODUCTION: A proportion of patients with multiple myeloma (MM) are older and/or have comorbidities, requiring dose adjustments. Data from OPTIMISMM (NCT01734928) supported the use of pomalidomide, bortezomib, and dexamethasone (PVd) for treating relapsed/refractory MM. This subanalysis of OPTIMISMM assessed outcome by frailty and/or bortezomib dose adjustment. METHODS: Patient frailty (nonfrail vs. frail) was classified using age, Charlson Comorbidity Index, and Eastern Cooperative Oncology Group performance status. Data from patients requiring a bortezomib dose reduction, interruption, and/or withdrawal during PVd treatment were assessed. RESULTS: Among 559 patients, 93 of 281 (33.1%) and 93 of 278 (33.5%) patients who received PVd and bortezomib and dexamethasone (Vd), respectively, were frail. Overall response rate (ORR) and median progression-free survival (PFS) were higher in nonfrail vs. frail with PVd treatment (ORR, 82.8% vs. 79.6%; PFS, 14.7 vs. 9.7 months); significantly higher than with Vd regardless of frailty. Grade ≥ 3 treatment-emergent adverse events (TEAEs) were higher with PVd vs. Vd, regardless of frailty. Discontinuations of PVd were lower in nonfrail vs. frail patients (19.2% vs. 30.1%); the median duration of treatment was similar (DoT; 8.8 vs. 8.9 months, respectively). Patients who received PVd with a bortezomib dose adjustment (n = 240) had a longer median DoT (9.3 vs. 4.5 months) and PFS (12.1 vs. 8.4 months) vs. those without. CONCLUSION: Frail patients treated with PVd demonstrated a higher ORR and a longer PFS and DoT vs. Vd, despite a higher frequency of grade ≥ 3 TEAEs leading to pomalidomide, bortezomib, and/or dexamethasone discontinuation. Therefore, PVd treatment may improve patient outcomes, regardless of frailty.

Increasing serum complement component 1q is associated with worse prognosis in advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a single-center, retrospective study.

Background: There is a lack of readily available clinical markers of non-small cell lung cancer (NSCLC) immunotherapy efficacy. Previous studies have found that overexpressed complement component 1q (C1q) promotes macrophage M2 polarization and an immunosuppressive tumor microenvironment. This study aimed to evaluate the association between serum C1q and the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC. Methods: A total of 168 patients with advanced NSCLC who received ICIs in the Renmin Hospital of Wuhan University were included in this study. Serum C1q levels were collected before and 3 weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. The primary outcome was overall survival (OS) (months from first dose of ICIs to death, censored at date of last follow-up). Secondary outcome was progression-free survival (PFS) [defined as months from first dose of ICIs to clinical or radiographic progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death, censored at date of last follow-up] and objective response rate (ORR) which was defined as rate of complete response (CR) or partial response (PR) at best response by RECIST 1.1. Results: A total of 168 patients were included in this study, including 127 males (75.60%) and 41 females (24.40%). Thirty-nine patients achieved objective response (2 CR, 37 PR), and 111 patients (66.07%) had stable disease (SD) as best response. The ORR was 23.21% and the disease control rate was 89.28%. The upward trends of serum C1q levels between baseline and post-treatment were strongly associated with the shorter PFS [hazard ratio (HR) =1.554, 95% confidence interval (CI): 1.07-2.10, P=0.01] and OS (HR =1.444, 95% CI: 1.01-1.98, P=0.03). Moreover, taking the median OS 18.9 months as the cut-off of prognosis, receiver operating characteristic (ROC) analysis showed that serum baseline C1q yielded an area under the ROC curve of 0.785 (95% CI: 0.711-0.869). The optimal serum baseline C1q cut-off point to predict immunotherapy prognosis was 216.2 mg/L. Conclusions: These findings suggested that elevated serum C1q after ICIs treatment was related to a worse prognosis in NSCLC. Monitoring the baseline and dynamic data of C1q during hospitalization showed the potential to predict the prognosis of NSCLC patients.

Prognostic value of systemic inflammation and for patients with colorectal cancer cachexia.

BACKGROUND: The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. METHODS: This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG-PS). Survival data were analysed using univariate and multivariate Cox regression analyses. RESULTS: The area under the curve, concordance index and survival analysis showed that C-reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non-cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08-5.32); high CAR, HR (95% CI) = 2.92 (1.88-4.55); high CRP, HR (95% CI) = 3.12 (2.08-4.67)] indicated a worse prognosis, compared with non-cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65-3.16); high CAR, HR (95% CI) = 2.36 (1.71-3.25); high CRP, HR (95% CI) = 2.58 (1.85-3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG-PS 2, HR (95% CI) = 1.61 (1.04-2.50); ECOG-PS 3/4, HR (95% CI) = 2.91 (1.69-5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG-PS 2, HR (95% CI) = 1.28 (0.90-1.81); ECOG-PS 3/4, HR (95% CI) = 2.41 (1.32-4.39]). Patients with CRC cachexia with an ECOG-PS score of 2 or 3-4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG-PS score of 0/1 and a low inflammation. CONCLUSIONS: The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG-PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG-PS in patients with CRC cachexia could provide a simple survival prediction.

Patients with brain metastases from gastric cancer.

INTRODUCTION: The aim of this study was to retrospectively evaluate the treatment strategies and possible prognostic factors in patients with brain metastases from gastric cancers. METHODS: We retrospectively reviewed 24 patients with brain metastases from gastric cancer who were treated at our center between January 2014 and March 2020. Clinicopathological characteristics and clinical outcomes were analyzed. RESULTS: The median follow-up time was six months (range, 1-40). The median survival time after diagnosis of brain metastases was six months (95% confidence interval: 1.33-10.66). The one- and two-year survival rates were 30.7% and 5.1%, respectively. On univariate analyses, absence of extracranial metastases was significantly associated with better overall survival (OS) but not intracranial progression-free survival (iPFS), while Eastern Cooperative Oncology Group performance status (ECOG PS), whole brain radiotherapy (WBRT) and systemic treatments were significantly associated with better iPFS and OS. Multivariate analysis showed that ECOG PS, extracranial disease and systemic treatments were independent prognostic factors, while only systemic treatment influenced the iPFS. Two patients achieved partial response, 12 patients had progressive disease, and 10 patients remained stable. Local tumor control in our series was achieved in 50%. One patient, who received a combination of camrelizumab and apatinib therapy following whole brain radiotherapy, achieved an obvious partial response. CONCLUSIONS: ECOG PS, extracranial disease and systemic treatments were independent prognostic factors for gastric cancer patients with brain metastases. The present best treatment for this group of patients was individual comprehensive therapy according to the different situation of each patient.

The relationship between clinicopathological variables, systemic inflammation, and CT-derived body composition with survival in patients with advanced non-small cell lung cancer receiving nivolumab as a second-line treatment.

BACKGROUND: Second-line immunotherapy is currently recognized to help only a subset of patients with advanced forms of non-small cell lung cancer (NSCLC). The current study analyzes the connection between prior treatment host/tumor characteristics and survival in advanced NSCLC patients receiving nivolumab as a second-line therapy. METHODS: A retrospective cohort analysis was carried out on individuals with advanced NSCLC receiving second-line Nivolumab with palliative intent between February 2016 and May 2019 across three health boards in NHS Greater Glasgow and Clyde, Lanarkshire, Ayrshire, and Arran in Scotland to examine the association between systemic inflammation, body composition, and survival were determined using computed tomography (CT). RESULTS: The current study investigates the connection between prior treatment host/tumor characteristics and survival in advanced NSCLC patients receiving nivolumab as a second-line therapy. The majority were 65 years of age or older (51%), female (53%), had adenocarcinoma (53%), and had good performance status (ECOG 0/1) (86%). Most patients had high SFI (70%) or VFA (54%). The median overall survival after starting Nivolumab was 15 months. ECOG-PS and hypoalbuminemia were significant predictors of 12-month survival in patients with advanced NSCLC following Nivolumab treatment, according to Cox regression (p-value = 0.047 and 0.014, respectively). CONCLUSION: In patients with advanced NSCLC receiving Nivolumab as a second-line therapy, ECOG-PS and hypoalbuminemia were strongly associated with survival. Systemic inflammation and hypoalbuminemia measurements may enhance the ECOG-PS stratification of expected outcomes.

Development of a Novel Predictive-Prognostic Scoring Index for Immune Checkpoint Inhibitors in Advanced Non-small Cell Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of patients with driver mutation absent advanced non-small cell lung cancer (NSCLC). The present study aimed to develop a reliable, reproducible, and practical scoring system to prognosticate and predict response to ICI response in patients with advanced NSCLC. PATIENTS AND METHODS: All patients who were diagnosed as having unresectable/advanced stage NSCLC and were treated with at least one cycle of ICIs at the Medical Oncology Departments of Dr. Burhan Nalbantoglu State Hospital (Nicosia, Cyprus) and Near East University Hospital (Nicosia, Cyprus) were included in the study. The association between variables and OS was evaluated using a Cox proportional hazards regression model. Variables with a P-value less than 0.05 in the univariate analysis were included in the multivariate model. A prognostic scoring system was developed.  Survival estimates were calculated using the Kaplan-Meier method. The value of the Concordance index (C-index) and the area under the curve (AUC) was used to evaluate the discriminative ability of scoring systems. RESULTS: One hundred fifty consecutive patients with unresectable/metastatic NSCLC who received PD-1 inhibitors between March 2017 and November 2022 were included. In the multivariate Cox regression model, serum lactate dehydrogenase (LDH), C-reactive protein (CRP) levels, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) were significantly associated with OS. We generated a new score using CRP ³1.0 mg/dL, ECOG PS ³2, and LDH level >ULN. Relative weight was based on the HRs of multivariate analyses (CRP ³1.0 mg/dL 2 points, ECOG PS ³2 2.5 points, and LDH level >ULN 1.5 points). The cohort was divided into three risk groups based on the sum of factors present: 0-2.5 (good risk), 3.5-4.5 (intermediate risk), or 6 (poor risk). The median OS was 18.9, 7.4, and 2.9 months for good, intermediate, and poor risk categories, respectively (log-rank test, p<0.001). The Harrell C-index of CEL to predict OS and PFS was 0.73 and 0.69, respectively, indicating significant predictability. The AUC of the scoring index for predicting the responses was 0.765 (95% CI: 0.685-0.845). CONCLUSION: The CEL score is a promising prognostic and predictive index consisting of serum CRP levels (C), ECOG PS (E), and serum LDH levels (L). This represents another step forward in the treatment of patients with advanced NSCLC.

Impact of Performance Status on Survival Outcomes and Health Care Utilization in Patients With Advanced NSCLC Treated With Immune Checkpoint Inhibitors.

Introduction: Landmark trials testing immune checkpoint inhibitors (ICIs) in advanced NSCLC are difficult to extrapolate to real-world practice given the exclusion of patients with poor (i.e., ≥2) Eastern Cooperative Oncology Group performance status (ECOG PS). We sought to evaluate the impact of ECOG PS on clinical outcomes and health care utilization in patients with NSCLC treated with ICIs in real-world practice. Methods: Patients with advanced NSCLC who received at least one dose of pembrolizumab or nivolumab were retrospectively identified from the Alberta Immunotherapy Database. The primary outcome was median overall survival, as stratified by ECOG PS. Secondary outcomes included median time-to-treatment failure and metrics of health care utilization, including emergency department visits, hospitalizations, and death in hospital. Results: A total of 790 patients were included, with 29.2% having poor ECOG PS at initiation of ICI. These patients had significantly lower median overall survival (3.3 versus 13.4 mo) and median time-to-treatment failure (1.4 versus 4.9 mo) compared with those with favorable ECOG PS (p < 0.0001 for both outcomes). Patients with poor ECOG PS were also more likely to present to the emergency department, be admitted to the hospital, and die in the hospital during their first admission (risk ratio = 1.6, 2.3-2.7, p < 0.001). Conclusions: Patients with NSCLC with poor ECOG PS treated with ICI had significantly worse survival outcomes and were significantly more likely to use health care services than those with favorable ECOG PS. The large proportion of patients with poor ECOG PS further justifies the urgent need for randomized trials evaluating the efficacy of ICI in this high-risk population.

The impact of ECOG performance status on efficacy of immunotherapy and immune-based combinations in cancer patients: the MOUSEION-06 study.

ECOG performance status (PS) is a pivotal prognostic factor in a wide number of solid tumors. We performed a meta-analysis to assess the role of ECOG PS in terms of survival in patients with ECOG PS 0 or ECOG PS 1 treated with immunotherapy alone or combined with other anticancer treatments. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, all phase II and III randomized clinical trials that compared immunotherapy or immune-based combinations in patients with solid tumors were retrieved. The outcomes of interest were overall survival (OS) and progression-free survival (PFS). We also performed subgroup analyses focused on type of therapy (ICI monotherapy or combinations), primary tumor type, setting (first line of treatment, subsequent lines). Overall, 60 studies were included in the analysis for a total of 35.020 patients. The pooled results showed that immunotherapy, either alone or in combination, reduces the risk of death or progression in both ECOG PS 0 and 1 populations. The survival benefit was consistent in all subgroups. Immune checkpoint inhibitors monotherapy or immune-based combinations are associated with improved survival irrespective of ECOG PS 0 or 1. Clinical trials should include more frail patients to assess the value of immunotherapy in these patients.

Real-World Data of Combined Immunochemotherapy in Patients With Nonsquamous Advanced NSCLC. A Single-Center Retrospective Study.

Introduction: On the basis of the landmark trial KEYNOTE-189 (KN-189), pembrolizumab plus chemotherapy has become the standard-of-care first-line treatment for patients with advanced nonsquamous NSCLC without oncogenic driver alterations.KN-189 included a selected patient population and lacks external validity. In clinical practice, many patients do not meet the inclusion criteria of KN-189, although they are treated accordingly. It is unknown whether these patients benefit equally as the trial population. Methods: We retrospectively analyzed all patients with advanced nonsquamous NSCLC without targetable oncogenic alterations who received the KN-189 treatment regimen between April 2018 and May 2021 at the University Hospital Basel, Switzerland. Patients were grouped into those who retrospectively met the inclusion criteria of KN-189 (group A) and those who did not (group B). Outcome parameters included progression-free survival (PFS), overall survival (OS), and objective response rate. Multivariate subgroup analyses were performed. Results: We identified 75 patients, including 29 patients in group A and 46 patients in group B. Median PFS was 9.2 and 4.6 months in group A and B, respectively (p = 0.12). Median OS was 16.5 and 6.5 months in group A and B, respectively (p = 0.11). Objective response rate was 59% in group A and 33% in group B (p = 0.03). Eastern Cooperative Oncology Group performance status greater than or equal to 2 and active infections were significantly associated with shorter PFS and OS. Conclusions: We report real-world data for patients treated according to the KN-189 regimen with inferior outcomes in patients who did not meet the KN-189 inclusion criteria. Better treatment options for this vulnerable patient population are needed.

Real-world predictors of survival in patients with extensive-stage small-cell lung cancer in Manitoba, Canada: a retrospective cohort study.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions. Objective: This real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada. Methods: A retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: <6 months; medium: 6-24 months; long: >24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models. Results: This analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and five-year OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1-2, and 16%, 3%, and 3% for those with ECOG PS 3-4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors - including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels - were less common but still seen in long-term survivors. Conclusion: Although rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ES-SCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future.

Impact of adjuvant sorafenib treatment after local ablation for HCC in the phase II SORAMIC trial.

Background & Aims: The aim of the study was to evaluate the efficacy and safety of adjuvant sorafenib treatment compared with placebo in patients with hepatocellular carcinoma who underwent local ablation. Methods: The SORAMIC trial is a randomised controlled trial with diagnostic, local ablation, and palliative sub-study arms. After initial imaging within the diagnostic study, patients were assigned to local ablation or palliative arms. In the local ablation cohort, patients were randomised 1:1 to local ablation + sorafenib vs. local ablation + placebo. The primary endpoint was time-to-recurrence (TTR). Secondary endpoints were local control rate and safety in terms of adverse events and quality-of-life. Results: The recruitment was terminated prematurely after 104 patients owing to slow recruitment. One patient was excluded because of a technical failure. Fifty-four patients were randomised to local ablation + sorafenib and 49 to local ablation + placebo. Eighty-eight patients who underwent standardised follow-up imaging comprised the per-protocol population. The median TTR was 15.2 months in the sorafenib arm and 16.4 months in the placebo arm (hazard ratio 1.1; 95% CI 0.53-2.2; p = 0.82). Out of 136 lesions ablated within the trial, there was no difference in local recurrence rate between sorafenib (6/69, 8.6%) and placebo groups (5/67, 5.9%; p = 0.792).Overall (92.5% vs. 71.4%, p = 0.008) and drug-related (81.4% vs. 55.1%, p = 0.003) adverse events were more common in the sorafenib arm compared with the placebo arm. Dose reduction because of adverse events were common in the sorafenib arm (79.6% vs. 30.6%, p <0.001). Conclusions: Adjuvant sorafenib did not improve in TTR or local control rate after local ablation in patients with hepatocellular carcinoma within the limitations of an early terminated trial. Impact and implications: Local ablation is the standard of care treatment in patients with early stages of hepatocellular carcinoma, along with surgical therapies. However, there is a risk of disease recurrence during follow-up. Sorafenib, an oral medication, is a routinely used treatment for patients with advanced hepatocellular carcinoma. This study found that sorafenib treatment after local ablation in people with early hepatocellular carcinoma did not significantly improve the disease-free period compared with placebo. Clinical trial number: EudraCT 2009-012576-27, NCT01126645.