Overall Survival Parameters Research Articles

Survival analysis after stereotactic ablative radiotherapy for early stage non-small cell lung cancer: a single-institution cohort study

BackgroundStereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality.MethodsFrom August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3–5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30–33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI).ResultsThe median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01–2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06–2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58).ConclusionSABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.

Identification of a Novel Prognostic Lymphangiogenesis-Related Signature Associated with Tumor Immunity for Guiding Therapy in Lung Adenocarcinoma

Lymphangiogenesis, an integral contributor to lymphatic metastasis, is a significant reason for the poor prognosis of cancer patients. Anti-lymphangiogenesis treatment is a promising novel therapeutic direction, especially for tumors resistant to conventional therapies. We confirmed the ectopic expression of lymphangiogenesis-related genes (LRGs) in lung adenocarcinoma (LUAD) cohorts based on the TCGA database. We constructed a prediction signature with 15 LRG prognostic signatures (F2RL1, LOXL2, MKI67, PTPRM, GPI, POSTN, INHA, LDHA, LINC00857, ITGA2, PECAM1, SOD3, GDF15, SIX1, and FGD5), and the overall survival (OS) was significantly different between the high- and low-risk groups (TCGA-training: p&lt;0.001, TCGA-test: p=0.02, GSE30219: p&lt;0.001, GSE37745: p=0.002, and GSE50081: p=0.002). Moreover, the risk score was also associated with the PIK3CA and BRCA1 pathways. In the nomogram, the prognostic prediction of the risk score was better than that of clinicopathologic parameters in OS, including age, sex, stage, T stage, N stage, and M stage. In summary, we constructed and validated a 15-LRG signature, which may help predict the prognosis of LUAD and offer a possible direction for future research on downstream molecular mechanisms.

Prognostic Value of Radiomic Analysis Using Pre- and Post-Treatment 18F-FDG-PET/CT in Patients with Laryngeal Cancer and Hypopharyngeal Cancer.

The prognostic value of conducting 18F-FDG PET/CT imaging has yielded different results in patients with laryngeal cancer and hypopharyngeal cancer, but these results are controversial, and there is a lack of dedicated studies on each type of cancer. This study aimed to evaluate whether combining radiomic analysis of pre- and post-treatment 18F-FDG PET/CT imaging features and clinical parameters has additional prognostic value in patients with laryngeal cancer and hypopharyngeal cancer. From 2008 to 2016, data on patients diagnosed with cancer of the larynx and hypopharynx were retrospectively collected. The patients underwent pre- and post-treatment 18F-FDG PET/CT imaging. The values of ΔPre-Post PET were measured from the texture features. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most predictive features to formulate a Rad-score for both progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curve analysis and Cox regression were employed to assess PFS and OS. Then, the concordance index (C-index) and calibration plot were used to evaluate the performance of the radiomics nomogram. Study data were collected for a total of 91 patients. The mean follow-up period was 71.5 mo. (8.4-147.3). The Rad-score was formulated based on the texture parameters and was significantly associated with both PFS (p = 0.024) and OS (p = 0.009). When predicting PFS, only the Rad-score demonstrated a significant association (HR 2.1509, 95% CI [1.100-4.207], p = 0.025). On the other hand, age (HR 1.116, 95% CI [1.041-1.197], p = 0.002) and Rad-score (HR 33.885, 95% CI [2.891-397.175], p = 0.005) exhibited associations with OS. The Rad-score value showed good discrimination when it was combined with clinical parameters in both PFS (C-index 0.802-0.889) and OS (C-index 0.860-0.958). The calibration plots also showed a good agreement between the observed and predicted survival probabilities. Combining clinical parameters with radiomics analysis of pre- and post-treatment 18F-FDG PET/CT parameters in patients with laryngeal cancer and hypopharyngeal cancer might have additional prognostic value.

Compartmental Syndecan-1 (CD138) expression as a novel prognostic marker in triple-negative metaplastic breast cancer

BackgroundMetaplastic breast cancer (MpBC) is rare, aggressive, and mostly triple-negative (TN) subtype of BC. We aimed to investigate the potential prognostic significance of Syndecan-1 (SDC1/CD138) expression in this unique tumor. MethodsArchived charts of 50 TNBC patients [21 MpBC and 29 invasive ductal carcinoma (IDC)] were retrospectively evaluated. Corresponding paraffin blocks were used for immunohistochemical (IHC) staining of SDC1. Compartmental (epithelial membranous, stromal, and cytoplasmic) staining scores were expressed in quartiles (Q) and correlated with disease-free survival (DFS) and overall survival (OS). ResultsThe median follow-up period was 54.6 months (range: 2.2–112.7). MpBC patients showed significantly worse DFS and OS than IDC (p = 0.007 and 0.004, respectively). MpBC demonstrated significantly higher Q4 stromal and membranous SDC1 compared to IDC (p = 0.016 and 0.021, respectively), whereas IDC exhibited significantly higher cytoplasmic Q4 SDC1 than MpBC (p = 0.015). Stromal Q4 SDC1 expression was found to be an independent factor associated with MpBC relative to IDC (OR: 6.7, 95% CI: 1.24–36.90; p = 0.028). Stromal Q4 SDC1 expression was also an independent prognostic parameter for worse DFS and OS compared to Q1–3 in the whole cohort (HR: 4.2, 95% CI: 1.6–10.5; p = 0.003 and HR: 5.8; 95% CI: 2.2–15.3; p < 0.001, respectively). In MpBC, cytoplasmic Q1–3 SDC1 expression was an independent prognostic indicator for worse OS compared with their IDC counterparts (HR: 2.837, 95% CI: 1.048–7.682; p = 0.04). ConclusionThis study suggests, for the first time, that differential expression and localization of SDC1 may contribute to the pathogenesis and prognosis of TN-MpBC. Therefore, targeting SDC1 (CD138) could emerge as a novel therapeutic approach for this devastating disease.

Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. Standard treatment includes chemoimmunotherapy with R-CHOP or similar regimens. Despite treatment advancements, many patients with DLBCL experience refractory disease or relapse. While baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameters have shown promise in predicting survival, they may not fully capture lesion heterogeneity. This study aimed to assess the prognostic value of baseline 18F-FDG PET radiomics features in comparison with clinical factors and metabolic parameters for assessing 2-year progression-free survival (PFS) and 5-year overall survival (OS) in patients with DLBCL.ResultsA total of 201 patients with DLBCL were enrolled in this study, and 1328 radiomics features were extracted. The radiomics signatures, clinical factors, and metabolic parameters showed significant prognostic value for individualized prognosis prediction in patients with DLBCL. Radiomics signatures showed the lowest Akaike information criterion (AIC) value and highest Harrell’s concordance index (C-index) value in comparison with clinical factors and metabolic parameters for both PFS (AIC: 571.688 vs. 596.040 vs. 576.481; C-index: 0.732 vs. 0.658 vs. 0.702, respectively) and OS (AIC: 339.843 vs. 363.671 vs. 358.412; C-index: 0.759 vs. 0.667 vs. 0.659, respectively). Statistically significant differences were observed in the area under the curve (AUC) values between the radiomics signatures and clinical factors for both PFS (AUC: 0.768 vs. 0.681, P = 0.017) and OS (AUC: 0.767 vs. 0.667, P = 0.023). For OS, the AUC of the radiomics signatures were significantly higher than those of metabolic parameters (AUC: 0.767 vs. 0.688, P = 0.007). However, for PFS, no significant difference was observed between the radiomics signatures and metabolic parameters (AUC: 0.768 vs. 0.756, P = 0.654). The combined model and the best-performing individual model (radiomics signatures) alone showed no significant difference for both PFS (AUC: 0.784 vs. 0.768, P = 0.163) or OS (AUC: 0.772 vs. 0.767, P = 0.403).ConclusionsRadiomics signatures derived from PET images showed the high predictive power for progression in patients with DLBCL. The combination of radiomics signatures, clinical factors, and metabolic parameters may not significantly improve predictive value beyond that of radiomics signatures alone.

Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis.

Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM tissue specimens compared with normal mesothelium. The objective of the current study was to further explore the role of FGF18 in PM and evaluate its suitability as a circulating biomarker. FGF18 mRNA expression was analyzed by real-time PCR in cell lines and in silico in datasets from the Cancer Genome Atlas (TCGA). Cell lines overexpressing FGF18 were generated by retroviral transduction and cell behavior was investigated by clonogenic growth and transwell assays. Plasma was collected from 40 PM patients, six patients with pleural fibrosis, and 40 healthy controls. Circulating FGF18 was measured by ELISA and correlated to clinicopathological parameters. FGF18 showed high mRNA expression in PM and PM-derived cell lines. PM patients with high FGF18 mRNA expression showed a trend toward longer overall survival (OS) in the TCGA dataset. In PM cells with low endogenous FGF18 expression, forced overexpression of FGF18 resulted in reduced growth but increased migration. Surprisingly, despite the high FGF18 mRNA levels observed in PM, circulating FGF18 protein was significantly lower in PM patients and patients with pleural fibrosis than in healthy controls. No significant association of circulating FGF18 with OS or other disease parameters of PM patients was observed. FGF18 is not a prognostic biomarker in PM. Its role in PM tumor biology and the clinical significance of decreased plasma FGF18 in PM patients warrant further investigation.

Methylated SEPT9 assay-based liquid biopsy as a biomarker in molecular targeted agent-treated hepatocellular carcinoma.

The development of molecular targeted agents (MTAs) has changed the treatment strategy for hepatocellular carcinoma (HCC). However, currently, there are no established predictive biomarkers for the treatment efficacy of MTAs. Previously, we developed a novel liquid biopsy test for HCC screening using sensitive methylated DNA testing of septin 9 gene (SEPT9). Here, we hypothesized that SEPT9 could be used as a biomarker for MTA treatment efficacy. We enrolled 157 patients receiving sorafenib or lenvatinib as a first-line therapy and allocated 85 and 72 patients to the training and validation cohorts, respectively. For the methylation assay, DNA was treated with methylation-sensitive restriction enzymes, followed by multiplex droplet digital PCR. Various clinical parameters were compared with clinical outcomes. The multivariate analysis revealed Eastern Cooperative Oncology Group performance status (≥ 1; p = 0.048), alpha-fetoprotein (AFP) (≥ 400ng/mL; p < 0.001), and methylated-septin-9 (m-SEPT9) (≥ 205 copies/mL; p = 0.018) as significant predictors of poor overall survival (OS) in the training cohort. m-SEPT9 was identified as a predictor of poor OS in the validation cohort. We developed a predictive score, called the MTA score, consisting of these three significant OS parameters (two points were added for AFP and one point for each of the other predictors). Patients with MTA scores ≥ 2 showed a significantly poor prognosis compared to those with MTA scores ≤ 1 in both the training and validation cohorts. m-SEPT9 could be a potential predictive biomarker for survival in patients with HCC treated with MTAs.

Development and validation of a scoring system incorporating tumor growth pattern and perineural invasion for risk stratification in colorectal cancer.

Tumor growth pattern (TGP) and perineural invasion (PNI) at the invasive margin have been recognized as indicators of tumor invasiveness and prognostic events in colorectal cancer (CRC). This study aims to develop a scoring system incorporating TGP and PNI, and further investigate its prognostic significance for CRC risk stratification. A scoring system, termed tumor-invasion score, was established by summing TGP and PNI scores. The discovery cohort (N = 444) and the validation cohort (N = 339) were used to explore the prognostic significance of the tumor-invasion score. The endpoints of the event were disease-free survival (DFS) and overall survival (OS) which were analyzed by the Cox proportional hazard model. In the discovery cohort, Cox regression analysis showed that DFS and OS were inferior for score 4 group compared with score 1 group (DFS, hazard ratio (HR) 4.44, 95% confidence interval (CI) 2.49-7.92, p < 0.001; OS, 4.41, 2.37-8.19,p < 0.001). The validation cohort showed similar results (DFS, 4.73, 2.39-9.37, p < 0.001; OS, 5.52, 2.55-12.0, p < 0.001). The model combining tumor-invasion score and clinicopathologic information showed good discrimination performance than single predictors. TGP and PNI were associated with tumor invasiveness and survival in CRC. The tumor-invasion score generated by TGP and PNI scores served as an independent prognostic parameter of DFS and OS for CRC patients.

Prognostic value of apparent diffusion coefficient in neuroendocrine carcinomas of the uterine cervix.

This research was designed to examine the associations between the apparent diffusion coefficient (ADC) values and clinicopathological parameters, and to explore the prognostic value of ADC values in predicting the International Federation of Gynecology and Obstetrics (FIGO) stage and outcome of patients suffering from neuroendocrine carcinomas of the uterine cervix (NECCs). This retrospective study included 83 patients with NECCs, who had undergone pre-treatment magnetic resonance imaging (MRI) between November 2002 and June 2019. The median follow-up period was 50.7 months. Regions of interest (ROIs) were drawn manually by two radiologists. ADC values in the lesions were calculated using the Functool software. These values were compared between different clinicopathological parameters groups. The Kaplan-Meier approach was adopted to forecast survival rates. Prognostic factors were decided by the Cox regression method. In the cohort of 83 patients, nine, 42, 23, and nine patients were in stage I, II, III, and IV, respectively. ADCmean, ADCmax, and ADCmin were greatly lower in stage IIB-IVB than in stage I-IIA tumours, as well as in tumours measuring ≥ 4 cm than in those < 4 cm. ADCmean, FIGO stage, and age at dianosis were independent prognostic variables for the 5-year overall survival (OS). ADCmin, FIGO stage, age at diagnosis and para-aortic lymph node metastasis were independent prognostic variables for the 5-year progression-free survival (PFS) in multivariate analysis. For surgically treated patients (n=45), ADCmax was an independent prognostic parameter for both 5-year OS and 5-year PFS. ADCmean, ADCmin, and ADCmax are independent prognostic factors for NECCs. ADC analysis could be useful in predicting the survival outcomes in patients with NECCs.

PATH-16. THRESHOLDS OF MITOTIC ACTIVITY AND POST-SURGERY RESIDUAL VOLUME ARE INDEPENDENT PROGNOSTIC FACTORS IN ASTROCYTOMA IDH-MUTANT

Abstract BACKGROUND The distinction between grade 2 and 3 is instrumental to choose between observational follow-up and adjuvant treatment in resected astrocytoma IDH-mutant. However, criteria for discriminating grade 2 and 3 tumors have not been updated since the WHO 2007 classification. There is no consensus on the method of evaluation of the mitotic activity or a mitosis cut-off for grading. The objectives were to evaluate the maximal mitotic activity on a series of resected astrocytoma IDH-mutant and assess its prognostic impact on survival. METHODS Maximal mitotic activity on consecutive high-power fields corresponding to 3 mm2 was examined in 118 lower-grade astrocytomas IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity as well as other prognostic factors (including age, performance status, presurgical tumor volume, plurilobar involvement, postsurgical residual tumor volume, midline involvement) was assessed in tumors with (i) ATRX loss, and (ii) without CDKN2A homozygous deletion, lesional enhancement, histological necrosis nor microvascular proliferation. RESULTS Among the 75 (64%) tumors which had gone through observational follow-up after resection, maximal mitotic activity, post-surgical residual volume and plurilobar involvement were independent prognostic factors of TTT (p &amp;lt; 0.0001). A threshold of mitotic activity for grade 2 was fitted using TTT and OS parameters. Using this threshold, patients with “grade 2 tumors” had a median TTT of 55 months versus 19 months for “grade 3” (p= 0.0057) and a median OS of 102 months versus 73 months respectively (p= 0.001). Residual volume &amp;lt; 1 cm3 was associated with longer OS (113 months versus 88 months, p= 0.0021). CONCLUSIONS The combination of mitotic activity and postsurgical residual volume improves prognostication in resected astrocytoma IDH-mutant. This novel risk assessment method could identify the best candidates for observational follow-up.

Elderly Patients with Head-and-Neck Squamous Cell Carcinoma: A Comparison between Surgery and Primary (Chemo)radiation

<h3>Purpose/Objective(s)</h3> Given the higher frequency of comorbidities and frailty, the optimal management of elderly patients with head-and-neck squamous cell carcinoma (HNSCC) is challenging. As randomized trials comparing surgery versus primary (C)RT for this patient population are difficult to perform, we aimed to compare the oncological outcomes between upfront surgery and definitive (C)RT within a large tertiary cancer center. <h3>Materials/Methods</h3> Elderly HNSCC patients (≥65 years) without distant metastases treated with upfront surgery or definitive (C)RT between 2010 and 2020 at a tertiary treatment center were included. Patient characteristics and tumor parameters were compared between both treatment groups using t-tests, Fisher's exact tests and chi-square tests. Overall survival (OS) and progression-free survival (PFS) were calculated, and Cox proportional hazard regression analyses of patient- und tumor-related variables were performed to assess the influence of the choice of primary treatment on survival. <h3>Results</h3> A total of 430 elderly HNSCC patients with a median age of 72 years met the inclusion criteria and were analyzed. Two hundred and seventy-six patients (64.2%) were treated with upfront surgery and risk-adapted adjuvant treatment, and 154 (35.8%) underwent primary (C)RT. Of the 276 patients treated with upfront surgery, 102 patients (37.0%) received adjuvant (C)RT, whereas 174 (63.0%) did not. Incomplete resection occurred in 11 cases (4.0% of the surgery group), while extracapsular spread was present in 33 patients (12.0%). Thirty-five patients (12.7% of the surgery group) received postoperative CRT. Patients receiving primary (C)RT exhibited a worse performance status, were more often smokers and had more often locoregionally advanced tumors (all <i>p</i><0.001). OS and PFS were superior in patients receiving surgery compared to patients treated by (C)RT (OS: HR=2.696, 95% CI 1.976-3.678, <i>p</i><0.001, PFS: HR=2.249, 95% CI 1.664-3.040, <i>p</i><0.001). Age, performance status, comorbidity burden, smoking status, T and N stage and HPV status were prognosticators for OS in the univariate analysis. In the multivariate analysis, choice of primary treatment (OS: HR=1.194, 95% CI 0.563-2.533, <i>p</i>=0.645, PFS: HR=1.112, 95% CI 0.564-2.194, <i>p</i>=0.760) did not constitute a significant parameter for OS or PFS. By restricting analysis to locoregionally advanced tumors (UICC=3-4, n=276), adjuvant (C)RT significantly improved OS compared to surgery alone (median OS: 68 vs. 97 vs. 103 months for surgery vs. surgery+adjuvant RT vs. surgery +postoperative CRT, respectively, <i>p</i><0.05 for surgery vs. surgery+adjuvant RT, <i>p</i>=0.07 for surgery+postoperative CRT). <h3>Conclusion</h3> In the multivariate analysis, upfront surgery with risk-adapted adjuvant treatment and primary (C)RT were comparable treatment approaches for elderly HNSCC patients in terms of oncological outcomes. Therefore, elderly HNSCC patients should be informed about both treatment options in order to ensure informed consent.

Dose-escalated re-irradiation improves outcome in locally recurrent head and neck cancer – Results of a large multicenter analysis

To determine efficacy and prognostic parameters of definitive re-irradiation of locoregionally recurrent squamous cell carcinoma of the head and neck (HNSCC). Materials and methodsPatients with locoregionally recurrent or second primary HNSCC undergoing re-irradiation with modern radiotherapy technique were eligible for this multicentric retrospective analysis. Main endpoints were overall survival (OS), progression-free survival (PFS) and locoregional control (LC). Univariate analyses were performed using the Kaplan Meier Method (log-rank). For multivariable analysis, Cox regression was used. ResultsA total of 253 patients treated between 2009 and 2020 at 16 university hospitals in Germany were included. The median follow up was 27.4 months (range 0.5–130). The median OS and PFS were 13.2 (CI: 10.7 – 15.7) months and 7.9 (CI: 6.7 – 9.1) months, respectively, corresponding to two-year OS and PFS rates of 29 % and 19 %. Rates of locoregional progression and “in-field-failure” were 62 % and 51 % after two years. Multivariable Cox regression analysis identified good ECOG performance status and high radiation dose as independent prognostic parameters for OS. Doses above 50 Gy (EQD2) achieved longer median OS of 17.8 months (vs 11.7 months, p < 0.01) and longer PFS of 9.6 months (vs 6.8 months, p < 0.01). In addition, there was a trend for worse survival in patients with tracheostomy (multivariable, p = 0.061). Concomitant systemic therapy did not significantly impact PFS or OS. ConclusionRe-irradiation of locally recurrent or second primary HNSCC is efficient, especially if doses above 50 Gy (EQD2) are delivered. ECOG performance score was the strongest prognostic parameter for OS and PFS.

Impact of perioperative red blood cell transfusion, anemia of cancer and global health status on the prognosis of elderly patients with endometrial and ovarian cancer.

IntroductionPerioperative red blood cell (RBC) transfusions have been associated with increased morbidity and worse oncological outcome in some solid neoplasms. In order to elucidate whether RBC transfusions themselves, the preoperative anemia of cancer (AOC), or the impaired global health status might explain this impact on patients with endometrial cancer (EC) or ovarian cancer (OC), we performed a retrospective, single-institution cohort study.Materials and methodsWomen older than 60 years with EC or OC were included. The influence of RBC transfusions, AOC, and frailty status determined by the G8 geriatric screening tool (G8 score), as well as the clinical-pathological cancer characteristics on progression-free survival (PFS) and overall survival (OS), was determined by using the Kaplan-Meier method and the Cox regression analyses.ResultsIn total, 263 patients with EC (n = 152) and OC (n = 111) were included in the study. Patients with EC receiving RBC transfusions were faced with a significantly shorter 5-year PFS (79.8% vs. 26.0%; p < 0.001) and 5-year OS (82.6% vs. 25.7%; p < 0.001). In multivariable analyses, besides established clinical-pathological cancer characteristics, the RBC transfusions remained the only significant prognostic parameter for PFS (HR: 1.76; 95%-CI [1.01–3.07]) and OS (HR: 2.38; 95%-CI [1.50–3.78]). In OC, the G8 score stratified the cohort in terms of PFS rates (G8-non-frail 53.4% vs. G8-frail 16.7%; p = 0.010) and AOC stratified the cohort for 5-year OS estimates (non-anemic: 36.7% vs. anemic: 10.6%; p = 0.008). Multivariable Cox regression analyses determined the G8 score and FIGO stage as independent prognostic factors in terms of PFS (HR: 2.23; 95%-CI [1.16–4.32] and HR: 6.52; 95%-CI [1.51–28.07], respectively). For OS, only the TNM tumor stage retained independent significance (HR: 3.75; 95%-CI [1.87–7.53]).DiscussionThe results of this trial demonstrate the negative impact of RBC transfusions on the prognosis of patients with EC. Contrastingly, the prognosis of OC is altered by the preoperative global health status rather than AOC or RBC transfusions. In summary, we suggested a cumulatively restrictive transfusion management in G8-non-frail EC patients and postulated a more moderate transfusion management based on the treatment of symptomatic anemia without survival deficits in OC patients.

Prognostic and clinicopathologic significance of circZFR in multiple human cancers

BackgroundAbnormally expressed in diverse cancers, circZFR has been correlated with clinical outcomes of cancer patients. Aim of this meta-analysis was to elucidate the prognostic role of circZFR in multiple human malignancies.MethodsLiterature retrieval was conducted by systematically searching on Pubmed, Web of Science, and the Cochrane Library up to December 2nd, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). The reliability of the pooled results was assessed through sensitivity analysis and the publication bias was measured by Begg’s and Egger’s test.ResultsA total of seventeen studies comprising 1098 Chinese patients were enrolled in this meta-analysis. Results demonstrated that high circZFR expression was correlated with an unfavorable OS (HR = 2.14, 95% CI 1.74, 2.64). High circZFR expression predicted larger tumor size (OR = 2.79, 95% CI 1.52, 5.12), advanced clinical stage (OR = 3.38, 95% CI 1.49, 7.65), tendentiousness of lymph node metastasis (LNM) (OR = 3.08, 95% CI 2.01, 4.71), and malignant grade (OR = 3.18, 95% CI 1.09, 9.30), but not related to age, gender, and distant metastasis (DM).ConclusionsHigh circZFR expression was associated with unfavorable OS and clinicopathologic parameters including tumor size, clinical stage, LNM, and histology grade, implicating a promising prognostic factor in cancers.

A Novel Prognostic Score Including the CD4/CD8 for AIDS-Related Lymphoma.

BackgroundA simple and clinically applicable prognostic scoring system for AIDS-related lymphoma (ARL) in the era of combination antiretroviral therapy (cART) is needed to better stratify patients’ risks and to assist in the decision-making of therapeutic strategies.MethodsWe conducted a retrospective multicenter cohort study in 138 primary ARL patients over an 8-year period from 2013 to 2020. Survival curves were estimated using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard models were performed to identify the association between patient-, lymphoma-, and HIV-specific variables with progression-free survival (PFS) and overall survival (OS). The incremental prognostic value of novel inflammatory biomarkers in the International Prognostic Index (IPI) was evaluated by comparing the receiver operating characteristic (ROC) curves, the concordance index (C-index), and the integrated Brier score (IBS).ResultsThe median age was 49.14 ± 14.20 (range 18–79) years, 81.9% were men, and the median follow-up was 44.94 (95% CI = 37.05–52.84) months. The 3-year OS and PFS were 39.4% (95% CI = 16.3–21.2) and 38.7% (95% CI = 14.5–19.7), respectively. We found that age, extranodal sites, bulky mass, CD4 T-cell counts, CD4/CD8 ratio, and hypoalbuminemia were associated with OS (all P < 0.05) at both univariate and multivariate analyses. Of the new inflammatory markers, only the CD4/CD8 ratio was an independent prognostic parameter of OS and PFS. A lower CD4/CD8 ratio was strongly associated with adverse clinical factors, including older age, advanced Ann Arbor stage, more extranodal sites, elevated erythrocyte sedimentation rate, prior history of HIV, higher red cell distribution width ratio, hypoproteinemia, and emaciation. When the CD4/CD8 ratio was added to the IPI, the composite HIV-IPI score showed significantly better discrimination than IPI alone [AUC (95% CI): HIV-IPI, 0.83 (0.77–0.89) vs. IPI, 0.72 (0.70–0.85)]. The HIV-IPI model provided good predictive performance [C-index (95% CI): HIV-IPI, 0.82 (0.81–0.83) vs. IPI, 0.75 (0.73–0.77), P < 0.001] and a satisfactory calibration function.ConclusionsThe CD4/CD8 ratio, an inexpensive and readily available marker, is a powerful independent prognostic parameter in patients with ARL. Furthermore, when the CD4/CD8 ratio is used in combination with IPI, it increases prognostic ability. The useful prediction of expected outcomes in ARL can inform treatment decisions.

18F-FDG PET/CT-Based Prognostic Survival Model After Surgery for Head and Neck Cancer.

The aims of this multicenter study were to identify clinical and preoperative PET/CT parameters predicting overall survival (OS) and distant metastasis-free survival (DMFS) in a cohort of head and neck squamous cell carcinoma patients treated with surgery, to generate a prognostic model of OS and DMFS, and to validate this prognostic model with an independent cohort. Methods: A total of 382 consecutive patients with head and neck squamous cell carcinoma, divided into training (n = 318) and validation (n = 64) cohorts, were retrospectively included. The following PET/CT parameters were analyzed: clinical parameters, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, and distance parameters for the primary tumor and lymph nodes defined by 2 segmentation methods (relative SUVmax threshold and absolute SUV threshold). Cox analyses were performed for OS and DMFS in the training cohort. The concordance index (c-index) was used to identify highly prognostic parameters. These prognostic parameters were externally tested in the validation cohort. Results: In multivariable analysis, the significant parameters for OS were T stage and nodal MTV, with a c-index of 0.64 (P < 0.001). For DMFS, the significant parameters were T stage, nodal MTV, and maximal tumor-node distance, with a c-index of 0.76 (P < 0.001). These combinations of parameters were externally validated, with c-indices of 0.63 (P < 0.001) and 0.71 (P < 0.001) for OS and DMFS, respectively. Conclusion: The nodal MTV associated with the maximal tumor-node distance was significantly correlated with the risk of DMFS. Moreover, this parameter, in addition to clinical parameters, was associated with a higher risk of death. These prognostic factors may be used to tailor individualized treatment.

Development and External Validation of a Prognostic Classifier for Elderly Head-and-Neck Cancer Patients Undergoing (Chemo)radiation

Elderly head-and-neck squamous cell carcinoma (HNSCC) patients form a heterogeneous cohort, and survival estimation is often challenging due to underlying comorbidities. Prognostic classifiers and nomograms may therefore be useful for overall survival (OS) estimation in order to provide shared decision-making in the clinical routine.A total of 284 elderly HNSCC patients aged ≥65 years who received a curative (chemo)radiation between 2010 and 2020 at a tertiary cancer center were used for the development of a survival classifier. On the basis of a multivariate Cox regression analysis, significant parameters were identified for which points were given according to the beta regression values. The derived classifier was then validated in a second, external cohort consisting of 217 elderly HNSCC patients undergoing (chemo)radiation. Based on the cumulative data of 501 patients, a nomogram for the 2-year and 4-year OS was created. We then examined in a third independent cohort whether the classifier could also stratify the prognosis of surgically treated elderly HNSCC patients without adjuvant (chemo)radiation (n = 169).In the multivariate backward stepwise Cox regression with likelihood ratio tests using P < 0.1 as inclusion criterion, the Karnofsky Performance Status (KPS, HR = 2.654, P < 0.001), the age-adjusted Charlson Comorbidity Index (CCI, HR = 2.598, P < 0.001) and the pre-radiotherapy CRP serum concentration (HR = 1.634, P = 0.064) were significant prognostic parameters for OS. Following the beta regression values, a KPS ≤70% and a CCI ≥6 points were given 1 point, while a CRP concentration ≥5 mg/L was given 0.5 points. The median OS was 107 (0 points), 34 (0.5 points), 28 (1 point), 11 (1.5 points), 9 (2 points) and 6 months (2.5 points), respectively. In order to obtain considerably distinct prognostic subgroups, 3 prognostic groups were created: A favorable (0 points), an intermediate (0.5-2 points) and a poor (2.5 points) subgroup. While the median OS for the favorable group amounted to 107 months, it was 28 and 6 months for the intermediate and poor cohorts, respectively (P < 0.001, log-rank test). In the external cohort, the median OS was found to range at 130, 29 and 9 months for the favorable, intermediate and poor group, respectively (P = 0.005). Using the aggregated data of both cohorts, a nomogram based on the KPS, CCI and CRP was created for the 2-year and 4-year OS that exhibited a concordance index of 0.65 (Harrell's C). For the surgically treated cohort of elderly HNSCC patients, only the KPS ≤70% (HR = 5.950, P = 0.002) but not the CCI ≥6 points (HR = 1.937, P = 0.232) or the baseline CRP serum value (HR = 1.743, P = 0.328) were significant prognosticators.We developed and externally validated a clinically feasible survival score for elderly HNSCC patients undergoing (chemo)radiation. Both the score and nomogram may be useful aiding shared decision-making of radiation oncologists and medical oncologists treating elderly HNSCC patients.

Prognostic value of psoas major muscle density in patients with breast cancer metastases to bone: a retrospective single-center cohort study.

Although sarcopenia is associated with poor prognosis for cancer patients, the relationship between muscle quantity and quality, and prognosis of breast cancer patients with bone metastases is unclear. This study aims to evaluate the association of muscle parameters, muscle area and density, and overall survival (OS) from the diagnosis of bone metastases in breast cancer patients with bone metastases. This study retrospectively investigated the prognostic value of muscle area and density in 90 women who were diagnosed with breast cancer with bone metastases between September 2005 and June 2018. We measured psoas major muscle and paravertebral muscle area and density on single axial computed tomography images at the L3 level and subgrouped the patients into higher or lower groups for each muscle measurement, using median values as cutoffs. We evaluated associations between OS and muscle parameters, using a Cox proportional hazards model adjusted by age and prognostic score for bone metastases (modified Katagiri score). Median OS among patients with lower psoas major muscle density (25months) was significantly shorter than in the higher psoas major muscle density group (61months; hazard ratio: 1.79, 95% confidence interval: 1.01-3.16, P=0.045). However, muscle area and paravertebral muscle density were not associated with OS in this setting. Lower psoas major muscle density was a predictor of poor prognosis in patients with breast cancer metastases to bone. The association between psoas major muscle density and prognosis allows wider research into interventions that can prevent loss of muscle density.

A Novel Prognostic Marker for Primary CNS Lymphoma: Lactate Dehydrogenase-to-Lymphocyte Ratio Improves Stratification of Patients Within the Low and Intermediate MSKCC Risk Groups.

BackgroundPrimary central nervous system lymphoma (PCNSL) is a highly aggressive and rare extranodal non-Hodgkin lymphoma (NHL). The MSKCC and the IELSG scores represent the most widely used prognostic models, but many changes have occurred in therapeutic protocols since their development. Moreover, many PCNSL patients cannot be classified using the IELSG score. We thus aimed to create a novel, effective and feasible prognostic model for PCNSL.MethodsWe included 248 PCNSL patients diagnosed with PCNSL. Our primary endpoint was the overall survival (OS) and we used the receiver operating characteristic (ROC) analysis to determine the optimal prognostic cut-off value for LLR (lactate dehydrogenase-to-lymphocyte ratio), neutrophil-to-lymphocyte ratio (NLR) and derived neutrophil-to-lymphocyte ratio (dNLR). Variable associated with OS were evaluated by univariate and multivariate analyses. 124 out of 248 patients were randomly selected as the internal validation cohort.ResultsBy univariate analysis, an age >60 years, Eastern Cooperative Oncology Group performance status (ECOG PS) >1, treatment with radiotherapy alone, high-risk groups of Memorial Sloan Kettering Cancer Center (MSKCC) score, NLR >4.74, dNLR >3.29, and LLR >166.8 were significantly associated with a worse OS. By multivariate analysis, the MSKCC score and LLR were confirmed as independent prognostic parameters for poorer OS. OS, however, was not significantly different between low- and intermediate-risk groups according to the MSKCC score, while LLR proved to be prognostically relevant and was thus used to develop a novel, effective three-tier PCNSL scoring system. Of 124 patients, 84 patients with survival data and LLR data were successfully validated by newly established PCNSL LLR scoring system.ConclusionsIn the present study, we demonstrate that a high LLR represents an independent unfavorable prognostic parameter in PCNSL patients which can be integrated into an effective prognostic model.

Olaparib in combination with bevacizumab compared to bevacizumab monotherapy for the first-line maintenance treatment of advanced ovarian cancer: a cost-effectiveness analysis

<h3>Objectives:</h3> The addition of maintenance olaparib to bevacizumab (OLAP+BEV) demonstrated significant progression-free survival (PFS) benefit vs BEV alone in the randomized trial PAOLA-1 in advanced ovarian cancer patients with homologous recombination deficiency (HRD)-positive tumors. We aim to quantify the health and economic impact by evaluating the US cost-effectiveness of OLAP+BEV relative to BEV as a maintenance treatment for women with advanced ovarian cancer who had partial or complete response to first-line platinum-based chemotherapy and whose cancer is associated with HRD-positive status <h3>Methods:</h3> Our economic model was a cohort-level four state partitioned survival model with a lifetime horizon. States were progression-free, post first progression, post second progression, and death, modelled using first PFS (PFS1), second PFS (PFS2) and overall survival (OS) outcomes from the PAOLA-1 trial. This approach captured multiple progressions, and the differing health state utility after each progression. PFS1 was modelled through parametric mixture survival modeling to a landmark survival point at 5 years, beyond which, patients who have not progressed are assumed to experience all-cause mortality as the general population. PFS2 and OS were modelled by fitting standard parametric models, and time on treatment data was used directly from PAOLA-1, with a treatment cap of 24 months for OLAP and 15 months for BEV. The cost of HRD testing was calculated as unit cost divided by prevalence and was included as a one-time cost for OLAP+BEV arm. US-based health state utility values were analyzed by applying the methods developed by Pickard. The analyses were conducted from a US healthcare payer perspective, with an annual discount rate of 3%. We also explored the robustness of results using deterministic (DSA) and probabilistic sensitivity analysis. <h3>Results:</h3> At year 5, 45.1% and 16.9% patients remained PFS from OLAP+BEV and BEV arm, respectively. The results showed that compared with bevacizumab alone, OLAP+BEV led to a gain in quality-adjusted life years (2.89 QALYs gain) and life years (3.43 Lys gain) but resulted in higher costs, leading to a deterministic incremental cost-effectiveness ratio (ICER) of $75,276 per QALY. OLAP+BEV had an 87.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. DSA identified efficacy (PFS and OS parameters), subsequent treatment and utility values as key model drivers. <h3>Conclusions:</h3> OLAP+BEV is associated with LY and QALY gain, and is cost effective for US payers relative to BEV monotherapy for the treatment of women with advanced, HRD-positive ovarian cancer