Predictor Of Overall Survival Research Articles

Low Expression of Mitochondrial Ribosomal Protein S5 is Associated With Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma

Mitochondrial ribosomal protein S5 (MRPS5) is abnormally expressed in various tumor tissues and may be a key molecule for the regulation of tumors. Our aim is to investigate the relationship between the expression of MRPS5 in clear cell renal cell carcinoma (ccRCC) and the prognosis of patients. MRPS5 expression in fresh tumoral tissues and peritumoral tissues of patients with ccRCC was examined by quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemical staining, respectively. MRPS5 expression level in paraffin-embedded tumoral tissue samples with ccRCC was evaluated by immunohistochemical scoring criteria. The relationship between the expression of MRPS5 and the clinicopathological parameters and prognosis of patients with ccRCC was analyzed statistically. The expression of MRPS5 mRNA and protein in fresh tumoral tissues was lower than that in peritumoral tissues. Among 160 paraffin-embedded tumoral tissue samples, 99 cases (61.9%) showed high expression and 61 cases (38.1%) showed low expression of MRPS5. The expression level of MRPS5 was significantly correlated with T classification, TNM stage, and Fuhrman grade. Kaplan-Meier method and log-rank test indicated that patients with low MRPS5 expression had significantly poorer overall survival and recurrence-free survival than high MRPS5 expression. Multivariate analysis revealed that MRPS5 expression was an independent predictor of overall survival and recurrence-free survival, respectively. MRPS5 low expression was a risk factor for the prognosis of patients. The expression level of MRPS5 is significantly correlated with the postoperative survival status, which has the potential to be used as a novel prognostic biomarker for patients with ccRCC.

Added prognostic value of DCE blood volume imaging in patients with suspected recurrent or residual glioblastoma – a hybrid [18F]FET PET/MRI study

Abstract Background MRI cerebral blood volume (CBV) measurements improves diagnosis of recurrent gliomas. The study investigated the prognostic value of dynamic contrast enhanced (DCE) CBV imaging in treated IDH wildtype glioblastoma when added to MRI or amino acid PET. Methods Hybrid [18F]FET PET/MRI with 2CXM (2-compartment exchange model) DCE from 86 adult patients with suspected recurrent or residual glioblastoma were retrospectively analysed. High CBV tumour volume (VOLCBV), and contrast enhancing (VOLCE) and [18F]FET active tumour (VOLFET) volumes were delineated. Absolute and fractional high CBV subvolumes within VOLCE and VOLFET were determined. Associations with overall survival (OS) were assessed by Cox analysis. Results Adjusted for MGMT status and steroid all total tumour volumes were individually associated with shorter OS. Adding VOLCBV to VOLCE, or VOLFET only the effect of VOLCBV was prognostic of OS (HR 1.327, p=0.042 and 1.352, p=0.011, respectively). High CBV subvolume within both VOLCE and VOLFET, were associated with shorter survival (HR 1.448, p=0.042 and 1.416, p=0011, respectively), and the low CBV subvolumes with longer survival (HR 0.504, p=0.002 and 0.365, p=0.001, respectively). The fraction of VOLCE and VOLFET with high CBV was a strong predictor of OS with shorter median OS in upper vs lower tertiles (8.3 vs 14.5 months and 7.1 vs 15.6 months, respectively, both p<0.001). Conclusions The high CBV tumour volume was a strong prognosticator of survival and allowed for separation of high and low risk subvolumes underlining the heterogeneous physiological environment represented in the contrast enhancing or metabolically active tumour volumes of treated glioblastoma.

Effect of endometriosis on prognosis of ovarian clear cell carcinoma: a 10-year retrospective study

IntroductionEndometriosis is considered as a precancerous lesion for OCCC; however its prognostic significance remains controversial. This study aims to evaluate the prognostic significance of endometriosis in patients with ovarian clear cell carcinoma (OCCC) and analyze the impact of other clinical pathological features on prognosis. Additionally, we also assess the role of laparoscopic surgery and chemotherapy in OCCC, hoping to provide evidence for improving the clinical diagnosis and treatment of OCCC.MethodsA retrospective analysis was conducted on medical records of 105 OCCC patients diagnosed and treated at the Gynecologic Cancer Center of Hubei Cancer Hospital in China from 2013 to 2022. Based on the presence or absence of endometriosis, OCCC patients were divided into two groups: a group with ovarian endometriosis consisting of 44 cases (41.9%) (EC-positive group) and a group without ovarian endometriosis consisting of 61 cases (58.1%)(EC-negative group). Clinical pathological characteristics, progression-free survival (PFS), and overall survival (OS) were compared between the two groups.ResultsThere were no statistically significant differences between the two groups in terms of age, CA125, tumor size, FIGO stage, adjuvant chemotherapy regimen, or chemotherapy efficacy (P>0.05). Residual tumor after surgery, staging, site invasion involvement, presence of ascites, positive cytology in ascitic fluid, lymph node metastasis, and chemotherapy efficacy were predictive factors for recurrence among patients with statistical significance (P<0.10); chemotherapy efficacy remained as independent predictors for recurrence (P<0.05); staging and chemotherapy efficacy remained as independent predictors for survival (P<0.05). There was no statistically significant difference observed between both groups regarding OS or PFS.ConclusionIn this study, co-existing endometriosis was not a prognostic factor for survival in patients with OCCC. The most important predictors of OS and PFS were FIGO stage and chemotherapy sensitivity. The intrinsic link between endometriosis and OCCC requires larger, better-designed prospective studies to draw more definitive conclusions.

Real-world outcomes of diffuse large B-cell lymphoma treated with frontline R-CHOP(-like) regimens in an Asian multi-ethnic population.

Recent breakthrough advances in the treatment of DLBCL, such as the antibody-drug conjugate polatuzumab vedotin, have yielded clinical survival benefit over rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for the first time in 20 years since the advent of the rituximab era. We thus examine the outcomes of standard immunochemotherapy for DLBCL in our multi-ethnic Asian population, so as to determine the real-world clinical need to adopt new therapeutics in this disease entity. We conducted a retrospective study involving patients (n = 1071) diagnosed with DLBCL at the National Cancer Centre Singapore from 2010 to 2022, and treated with first-line rituximab-based regimens. The median follow-up duration was 48 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. The cohort consisted of 590 male and 481 female patients with a median age of 63.8 years (range, 19.3-93.6). Most were stage III-IV at diagnosis (60.9%) and of non-germinal center B-cell like (non-GCB) subtype by Han's criteria (56.5%). The vast majority received R-CHOP(-like) regimens (n = 997, 93.1%), including rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH-R) (n = 95), achieving a 5-year progression-free survival (PFS) and overall survival (OS) of 64.5% and 74.7% respectively. Male sex (p = 0.0294), age > 60 years (p < 0.0001), poor ECOG scores (2-4) (p < 0.0001), advanced stage (III-IV) (p < 0.0001), presence of B-symptoms (p = 0.0305), and raised LDH (p = 0.0161) were independent predictors of OS, 4 of which are risk factors in the International Prognostic Index (IPI). In the intermediate to high-risk subgroup (IPI scores 2-5; n = 752), the 5-year PFS and OS were only 59.0% and 69.8% respectively. EBV status, MYC and/or BCL2/BCL6 rearrangements, were not significantly associated with survival outcomes. EPOCH-R was used more frequently than R-CHOP in patients with MYC rearrangements (n = 82, p < 0.0001), including those with MYC/BCL2 double-hit genetics (n = 31, p < 0.0001). Notably, neither regimen significantly affected survival outcomes, both in MYC-rearranged (PFS: HR 0.60, p = 0.1704; OS: HR 0.49, p = 0.0852), and in MYC/BCL2 double-hit DLBCL (PFS: HR 1.30, p = 0.6433; OS: HR 1.02, p = 0.9803). Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.

Textbook oncological outcome of locally advanced gastric cancer patients with preoperative sarcopenia: a multicenter clinical study.

The impact of postoperative sarcopenia on the Textbook Oncological Outcome (TOO) in locally advanced gastric cancer (LAGC) remains uncertain. This study investigates the relationship between sarcopenia and TOO, explores its long-term prognostic value, and develops a prognostic model incorporating sarcopenia and TOO for survival prediction. We performed a retrospective analysis of clinical and pathological data from patients with LAGC who underwent radical surgery at two Chinese tertiary referral hospitals. Sarcopenia was defined as an SMI < 36.4 cm2/m2 in males and < 28.4 cm2/m2 in females. TOO was defined as the addition of perioperative chemotherapy to the textbook outcomes (TO). A nomogram was developed to predict postoperative overall survival (OS) and recurrence-free survival (RFS) in LAGC patients. The study included 972 patients with LAGC. The overall TOO achievement rate was 67.1%. The TOO achievement rate was significantly higher in patients non-sarcopenia compared to those with sarcopenia (68.9% vs. 61.1%, P = 0.031). Logistic regression revealed that age ≥ 65, high ASA score, and sarcopenia were independent risk factors for TOO failure. Cox regression analysis identified TOO, sarcopenia, tumor size, differentiation, vascular invasion, pT stage, and pN stage as independent predictors of OS and RFS. Nomogram models based on sarcopenia and TOO accurately predicted the 3-year and 5-year OS and RFS. Preoperative sarcopenia was an independent predictor of TOO implementation. A prognostic prediction model that integrates preoperative sarcopenia and TOO, which outperforms the current staging system, can aid clinicians in effectively assessing the prognosis of patients with LAGC.

Improved prognostication of overall survival after radiotherapy in lung cancer patients by an interpretable machine learning model integrating lung and tumor radiomics and clinical parameters.

Accurate prognostication of overall survival (OS) for non-small cell lung cancer (NSCLC) patients receiving definitive radiotherapy (RT) is crucial for developing personalized treatment strategies. This study aims to construct an interpretable prognostic model that combines radiomic features extracted from normal lung and from primary tumor with clinical parameters. Our model aimed to clarify the complex, nonlinear interactions between these variables and enhance prognostic accuracy. We included 661 stage III NSCLC patients from three multi-national datasets: a training set (N = 349), test-set-1 (N = 229), and test-set-2 (N = 83), all undergoing definitive RT. A total of 104 distinct radiomic features were separately extracted from the regions of interest in the lung and the tumor. We developed four predictive models using eXtreme gradient boosting and selected the top 10 features based on the Shapley additive explanations (SHAP) values. These models were the tumor radiomic model (Model-T), lung radiomic model (Model-L), a combined radiomic model (Model-LT), and an integrated model incorporating clinical parameters (Model-LTC). Model performance was evaluated through Harrell's concordance index, Kaplan-Meier survival curves, time-dependent area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis. Interpretability was assessed using the SHAP framework. Model-LTC exhibited superior performance, with notable predictive accuracy (C-index: training set, 0.87; test-set-2, 0.76) and time-dependent AUC above 0.75. Complex nonlinear relationships and interactions were evident among the model's variables. The integration of radiomic and clinical factors within an interpretable framework significantly improved OS prediction. The SHAP analysis provided insightful interpretability, enhancing the model's clinical applicability and potential for aiding personalized treatment decisions.

Exposure-Response Analyses of Sacituzumab Govitecan Efficacy and Safety in Patients With Metastatic Triple-Negative Breast Cancer.

Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for patients with metastatic triple-negative breast cancer (mTNBC) who received ≥2 prior systemic therapies (≥1 in metastatic setting). Exposure-response (E-R) relationships between SG exposure and efficacy and safety outcomes were characterized in 277 patients with mTNBC using data from the phase I/II IMMU-132-01 and phase III ASCENT (IMMU-132-05) studies. Evaluated endpoints included complete response (CR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety endpoints (individual first worst grade of select adverse events (AEs)). E-R analyses were also conducted for time to first dose reduction or delay. Patients received SG at 8 or 10 mg/kg intravenously on days 1 and 8 of a 21-day cycle. Average SG-related serum exposure over the treatment duration (until the event) was consistently the most significant exposure metric correlated with efficacy and safety endpoints. Higher average concentration over the treatment duration for SG (CAVGSG) was the best predictor of CR and ORR. The model-predicted proportions of patients with CR and ORR at 10 mg/kg were 4.26% and 32.6%, respectively. Higher CAVG for total antibody was the best predictor of OS and PFS. The model-predicted probability of OS at 12 months at median lactate dehydrogenase (227 IU/L) was 53%. The probability of grade ≥1 evaluated AEs and the risk of dose reductions and delays significantly increased with increasing CAVGSG. The model-predicted proportions of patients with any-grade AEs were 35.9%, 67.4%, 64.7%, and 67.1% for vomiting, diarrhea, nausea, and neutropenia, respectively (10 mg/kg dose group). Neutropenia was the only evaluated AE for which CAVGSG was significantly associated with grade ≥3 events. The clinically meaningful efficacy and manageable safety achieved with SG 10 mg/kg on days 1 and 8 of every 21-day cycle dosing regimen supports the appropriateness of this clinical dosage in patients with mTNBC.

PREDICTORS OF POSTOPERATIVE COMPLICATIONS AND FUNCTIONAL OUTCOMES IN PEDIATRIC PATIENTS WITH SURGICALLY TREATED FOURTH VENTRICLE TUMOR

Background Tumors of fourth ventricle are frequently treated pathologies in pediatric neurosurgery. Data regarding predictors for permanent neurological deficits, long-term functional outcomes, cerebellar mutism (CM), the extent of resection (EOR), and oncological outcomes are scarce. We attempt to contribute to this topic with analysis of our institutional cohort. Methods A retrospective single-center study of patients aged ? 19 years who underwent primary surgical resection of fourth ventricular tumor over a 15-year period (2006–2021). Predictors analyzed included: age, gender, surgical approach, anatomical pattern, tumor grade, EOR, tumor volume, and others as appropriate. Results 106 patients were included (64 males, mean age 7.3 years). Rate of permanent neurological deficit was 24.2%; lateral tumor extension (p = 0.036) and tumor volume greater than 38 cm3 (p = 0.020) were significant predictors. Presence of deficit was the only significant predictor of reduced (less than 90) Lansky score (p = 0.005). CM occurred in 20.8% of patients and was influenced by medulloblastoma histology (p = 0.011), lateral tumor extension (p = 0.017), and male gender (p = 0.021). No significant difference between transvermian and telovelar approach in development of CM was detected (p = 0.478). No significant predictor was found for EOR. EOR was not found to be significant predictor of overall survival for both low-grade and high-grade tumors, however, gross total resection (GTR) was protective against tumor recurrence compared to near-total or subtotal resection (p &lt; 0.001). Survival was found to be better in older patients (? 7.0 years, p = 0.019). Conclusion The overall rate of postoperative complications remains high due to the eloquent localization. Older patients (&gt;7 years) have been found to have better outcomes and prognosis. Achieving GTR whenever feasible and safe has been shown to be critical for tumor recurrence. CM was more common in patients with medulloblastoma, and in patients with tumors extending through the foramen of Luschka. The telovelar approach uses a safe and anatomically sparing corridor, however, it has not been associated with a lower incidence of CM and neurological sequelae in our series, showing that each case should be assessed on an individual basis.

Advantage of Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer.

Lymph node metastasis (LNM) is among the most important predictors of poor prognosis after surgery for gallbladder cancer (GBC). Traditionally, staging has been based on the raw count of LNM, with a high risk of understaging patients who undergo inadequate lymph node dissection (LND). The log odds of metastatic lymph nodes (LODDS) may represent an alternative staging approach to stratify patients more accurately after resection of GBC. In this cross-sectional study, patients who underwent curative-intent surgery with LND for GBC were identified from an international database. Two predictive models were built and compared, each integrating a different lymph nodes status indicator [i.e., American Joint Committee on Cancer (AJCC) and LODDS]. Among 199 patients, the median number of lymph nodes examined was 5 [interquartile range (IQR): 3.0, 8.0]; most patients had T1 (n = 26, 13.1%) or T2 (n = 97, 48.7%) disease, and a subset had LNM (n = 87, 44.0%). Multivariable Cox analysis demonstrated LODDS was an independent predictor of overall survival [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.5-2.3; p < 0.001]. The LODDS model demonstrated better performance compared with a traditional model that utilized the AJCC N category [concordance (C) index: 0.814 versus 0.763; p < 0.001]. Patients classified as high- versus low-risk based on LODDS had much worse overall survival (OS) (4.9% versus 83.7%, respectively; p < 0.001). The LODDS model performance remained high even among patients with inadequateLND (< 6 LN) (C index: 0.87). An online calculator was developed ( https://catalano-giovanni.shinyapps.io/LoddsGBC/ ). A novel prognostic model based on LODDS may overcome the inherent limitations of the current AJCC staging system, reducing understaging among patients with fewer than six total lymph nodes evaluated.

Serum lactate dehydrogenase as a prognostic marker for treatment response in IDH wild-type glioblastoma patients undergoing stupp protocol.

Elevated lactate dehydrogenase (LDH), a marker of tumor aggressiveness and metabolic alterations, may predict treatment response and overall survival across various tumors. This study investigates the correlation between serum LDH levels and clinical outcomes in glioblastoma patients treated with radiotherapy (RT) and temozolomide (TMZ). This retrospective study analysed patients with IDH wild-type glioblastoma (IDH-wt GB) treated at the Radiotherapy Department of Azienda Ospedaliero-Universitaria Senese from 2018 to 2023. Clinical data, including hematologic parameters (e.g., LDH), imaging (MRI), and MGMT promoter methylation status, were collected. All patients received RT and TMZ following the Stupp protocol. Serum LDH levels were measured one week before RT, and Radiological Response (RR) was assessed using RANO criteria. Overall survival (OS), progression-free survival (PFS), and RR were primary endpoints. Statistical analyses included Kaplan-Meier, Cox regression, and decision tree analysis for LDH cut-off determination. In a cohort of 147 IDH wild-type glioblastoma patients treated with the Stupp protocol, the median OS was 14 months and median PFS was 8 months. Elevated baseline LDH levels were associated with significantly poorer outcomes, showing a median OS of 9 months versus 20 months and a median PFS of 6 months versus 13 months for lower LDH levels (p < 0.001 and p = 0.0001, respectively). LDH levels also correlated with RR (p = 0,001), Multivariate analysis confirmed high LDH as an independent predictor of worse OS (HR = 2.31) and PFS (HR = 2.60), suggesting its utility as a prognostic biomarker. Elevated LDH levels before starting the Stupp protocol are clinically significant as they predict poorer overall survival and progression-free survival in glioblastoma patients and worse RR. Incorporating LDH measurements into treatment planning can help identify patients at higher risk of poor outcomes, allowing for more tailored and potentially aggressive treatment strategies to improve management and therapeutic responses in glioblastoma.

Development and validation of a dynamic nomogram for individualized prediction of survival in patients with colon cancer.

Current tools for predicting survival outcomes in colon cancer patients predominantly rely on clinical and pathologic characteristics. However, accumulating evidence demonstrates a significant correlation between nutritional status and patient outcomes. This study aimed to establish a new dynamic nomogram for individualized prediction of postoperative overall survival (OS). The clinicopathological and nutritional data of colon cancer patients undergoing radical resection were retrospectively collected and randomly divided into the primary and validation cohorts. Risk factors on OS rates were investigated by Cox analyses and, the nomogram was constructed using significant predictors. Among 1,024 patients, 341 deaths were observed after median follow-up of 54months. Five independent prognostic factors, including nutritional status assessments, were incorporated into the nomogram. The C-index regarding 1-, 3-, and 5-year OS were 0.830, 0.859, and 0.757 in the primary cohort and 0.843, 0.870, and 0.773 in the validation cohort, respectively. Calibration curves for the probability of OS exhibited an optimal agreement. Decision curve analyses revealed the greater application value of the nomogram than the TNM staging system. Based on the nomogram, patients could be stratified into three scenarios with significant prognostic classification (P < 0.0001). In conclusion, we developed and validated an easy-to-use dynamic nomogram for predicting postoperative OS in colon cancer patients.

MS O12 - HPB The efficacy of CA19-9 in predicting resectability and survival in pancreatic cancer patients with jaundice: A retrospective cohort study

Abstract Background Carbohydrate antigen 19-9 (CA19-9) is the most utilised biochemical marker in pancreatic ductal adenocarcinoma (PDAC); shown to be related to resectability and prognosis. However, concurrent cholestasis, commonly seen in PDAC, can also elevate CA19-9, which may lead to unreliability and hence limit its efficacy in jaundiced patients, making management planning and prognostication more challenging. This study aims to investigate the impact of jaundice on the efficacy of CA19-9 in predicting resectability and survival in PDAC patients. Method 715 patients undergoing attempted resection for PDAC between 2010-2023 were identified from a prospectively maintained surgical database for retrospective analysis. The ability of CA19-9 to predict resectability and survival in different bilirubin sub-groups was assessed using receiver operating characteristic and Kaplan-Meier curves. Existing adjustment methodologies were applied and the curves replotted to assess their effects on the predictive efficacy of CA19-9. Multivariate analysis was then utilised to screen other potentially predictive factors which could be incorporated in the future. Results Of the 554 (77.4%) patients who underwent resection, CA19-9 predicted resectability in the first three bilirubin subgroups: ≤21 µmol/l (AUROC:0.660, 95% CI:0.551-0.769, p=0.004), 21&amp;lt;x≤130 µmol/l (AUROC:0.689, 95% CI:0.595-0.784, p&amp;lt;0.001) and 130&amp;lt;x≤315 µmol/l (AUROC:0.710, 95% CI:0.614-0.807, p&amp;lt;0.001). However, CA19-9 did not predict resectability in patients with bilirubin levels &amp;gt;315 µmol/l (AUROC:0.579, 95% CI:0.452-0.707, p=0.222). CA19-9 was a significant predictor of overall survival in the non-jaundiced (p=0.048) cohort but did not predict survival in patients with bilirubin levels &amp;gt;21 µmol/l. Existing adjustment methodologies did not improve predictive efficacy of CA19-9 for resectability or prognosis. Conclusion These findings support the prospect of decreased ability of CA19-9 to predict resectability and survival in PDAC patients with jaundice. Further investigation is required to find a method of adjusting CA19-9 values based on jaundice to aid diagnostic and treatment decision making.

Abstract B044: Fragmentomic features of cell-free DNA predict late-stage melanoma treatment benefit and survival

Abstract The levels of circulating tumour DNA (ctDNA) in cancer patients are associated with response and survival outcomes. Analysis of ctDNA generally requires knowledge of tumour mutations or the application of expensive next generation targeted sequencing. Here we utilize a cutting-edge approach, combining cell-free DNA molecules (cfDNA) fragmentomics and machine learning, to infer the presence of ctDNA to predict response and survival to immune checkpoint inhibitors in stage III unresectable and IV melanoma patients. Genome libraries were constructed from cfDNA derived from 48 (discovery cohort) and 96 (validation cohort) stage III unresectable and IV melanoma patients prior to the commencement of immune-checkpoint inhibitors. The discovery cohort included any-line therapy, patients had a median age of 66, 69% were male, 33% were BRAF V600 mutant, and 88% had an ECOG of 0-1. The validation cohort included first-line therapy, patients had a median age of 69, 59% were male, 22% were BRAF V600 mutant, and 89% had an ECOG of 0-1. Genome libraries were subjected to shallow whole genome sequencing (8x) and the following metrics were calculated: tumour content prediction, aneuploidy levels, various proportions of fragments ranging from 20 bp to 320 bp, the proportion of mitochondrial DNA, and the amplitude of 10 bp size oscillations between 75-150 bp, and the Shannon diversity of trinucleotide motifs at each end of the read. Non-penalized logistic modelling was used to predict clinical benefit, and the resulting logistic model was transformed into a “white-box” model. The white-box model was applied to the cohorts and used to test progression-free and overall survival. The removal of reads with inserts &amp;lt;90 and &amp;gt;150 bp greatly improved chromosome aneuploidy detection from 19% to 31%. Logistic modelling of the fragmentomic features of cfDNA yielded an AUROC of 0.83 for prediction of clinical benefit in the discovery cohort. A cutoff was set for the fragmentomic model score and used to stratify groups for survival analysis. Patients with a low score showed significantly worse progression- free (mPFS 931 vs 286 days, HR 3.4, 95% CI 1.55-7.46, p&amp;lt;0.002) and overall (mOS NR vs 363 days, HR 8.1, 95% CI 2.7-24.3, p&amp;lt;0.001) survival. These results were replicated in the validation cohort with an AUROC of 0.78 for prediction of clinical benefit and significant associations with progression-free (mPFS 1986 vs 926 days, HR 2.33 95% CI 1.27-3.92, p=0.005) and overall (mOS NR vs 1238 days, HR 4.51 95% CI 1.7-11.96, p=0.002) survival. Fragmentomic features of plasma cfDNA enable the prediction of clinical benefit, progression-free, and overall survival in stage IV melanoma patients treated with immune-checkpoint inhibitors. Citation Format: Aaron B Beasley, Leslie Calapre, Ashleigh Stewart, Anna L Reid, Russell Diefenbach, Wei Yen Chan, Rebecca Auzins, Luisa Pinnel, Sanjeev Adhikari, Muhammad A Khattak, Peter Lau, Tarek M Meniawy, Jenny H Lee, Lydia Warburton, Michael Millward, Alexander M Menzies, Richard A Scolyer, Georgina V Long, Helen Rizos, Elin S Gray. Fragmentomic features of cell-free DNA predict late-stage melanoma treatment benefit and survival [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B044.

Significance of the geriatric nutritional risk index and neutrophil-to-lymphocyte ratio as prognostic indicators in older patients with gastric cancer: a retrospective cohort study.

The number of older patients with cancer is increasing with the progression of aging societies. In the current study, we sought to clarify the prognostic values of the geriatric nutritional risk index (GNRI) as a nutritional index and the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory index in older patients with gastric cancer. Between January 2007 and December 2016, a total of 197 consecutive gastric cancer patients aged ≥ 75 years who underwent radical gastrectomy were enrolled in this study. The prognostic values of preoperative GNRI and NLR were assessed using time-dependent receiver operating characteristic curve analysis, log-rank tests, and Cox regression analysis. The areas under the curve (AUCs) predicting 5-year overall survival (OS) were 0.668 for GNRI and 0.637 for NLR. The 5-year OS rates in the groups with low GNRI and NLR were 40.1% and 74.1% (p < 0.001), and those with high GNRI and NLR were 70.7% and 41.5% (p < 0.001), respectively. Multivariate analysis showed that GNRI (hazard ratio (HR): 0.584; 95% confidence interval (CI): 0.356-0.960; p = 0.034) and NLR (HR: 2.470; 95% CI: 1.503-4.059; p < 0.001) were independent predictors for OS. The GNRI-NLR score constructed with GNRI and NLR had a higher AUC (0.698) than those of GNRI or NLR alone and was an independent prognostic factor (HR, 0.486; 95% CI: 0.363-0.651; p < 0.001). GNRI and NLR are useful prognostic biomarkers in older patients with gastric cancer aged≥75 years. The GNRI-NLR score could contribute to a more personalized and holistic approach to cancer treatment in this patient population.

Abstract 4118178: Echocardiographic Measure of Right Ventricular-Pulmonary Arterial Coupling Predicts Survival in Lung Cancer

Background: Echocardiographic indicators of pulmonary hypertension have been reported to predict decreased survival in lung cancer. We sought to test the hypothesis that this may be associated with impaired right ventricular (RV)-systolic pulmonary arterial pressure (sPAP) coupling, further enhancing the prognostic strength of echocardiography in lung cancer. Methods: This prospective observational study included 220 patients with non-small cell lung cancer (NSCLC) examined by Doppler, strain and 3D echocardiography before starting therapy. Prediction of overall survival was assessed by univariable analysis followed by multivariate Cox regression, receiver operating characteristic (ROC) curves and Kaplan-Meier analyses. Results: Echocardiographic examination was on average within normal limits, even though 30% of the patients had sPAP ≥35 mm Hg. In univariable analysis, overall survival was associated with measures of RV systolic function and probability of pulmonary hypertension. In multivariate Cox regression, only RV global longitudinal strain (GLS)/sPAP (HR: 5.766 [95% CI: 1.025–32.443]) and Eastern Cooperative Oncology Group performance status &lt;2 (HR: 0.332 [95% CI: 0.171–0.644]) independently predicted survival. The optimal ROC curve-derived RV GLS/sPAP cut-off to predict survival was −0.54%/mm Hg. Among patients in Union for International Cancer Control (UICC) stage 4, those with impaired RV-arterial coupling (RV GLS/sPAP &gt;−0.54%/mm Hg) had worse survival than those with maintained RV-arterial coupling (HR: 2.8 [95% CI: 1.5–5.3]); the latter subgroup had similar survival compared with patients in UICC stage 3 (HR: 0.57 [95% CI: 0.28–1.14]). Conclusion: RV GLS/sPAP as an echocardiographic measure of RV-arterial coupling adds to prognostication by the UICC status in NSCLC.

Comprehensive data of 5085 patients newly diagnosed with colorectal liver metastasis between 2013 and 2017: Fourth report of a nationwide survey in Japan.

The Joint Committee for Nationwide Survey on colorectal liver metastasis (CRLM) was established to improve treatment outcomes in patients with CRLM. The aim of this study was to evaluate the transition in the characteristics and treatment strategies of patients with CRLM and to analyze the prognostic factors. The data of 5085 patients newly diagnosed between 2013 and 2017 were compared with those of 3820 patients from 2005 and 2007. In patients who underwent hepatectomy (n = 2759 and 2163), the number of CRLMs was significantly higher and in the 2013-2017 data than in the 2005-2007 data (median 2 vs. 1; p = .005). Overall survival (OS) rates after diagnosis of CRLM after hepatectomy were better in the 2013-2017 data than that in the 2005-2007 data (5-year OS, 62.4% vs. 56.7%, p < .001). Recurrence-free survival (RFS) after hepatectomy was comparable between the groups (5-year RFS, 30.5% vs. 30.7%; p = .068). Multivariate analyses identified age at diagnosis of CRLM ≥70 years, lymph node metastasis of primary lesion, preoperative carbohydrate antigen (CA) 19-9 value >100 U/mL, number of CRLM 2-4, and R2 resection as independent predictors of OS. Synchronous CRLM, concomitant extrahepatic metastasis, lymphatic invasion, lymph node metastasis of primary lesion, preoperative CA19-9 value >100 U/mL, number of CRLM 5-, and nonlaparoscopic approach were selected as that of RFS. Despite having a higher prevalence of advanced stage CRLM in the 2013-2017 patient population compared to the 2005-2007 cohort, prognostic outcomes demonstrably improved in the later period.

The role of chemotherapy in the management of pancreatic acinar cell carcinoma.

Pancreatic acinar cell carcinoma (pACC) is a rare malignancy with unique clinical and molecular features. The role of chemotherapy in pACC management is not well established. The National Cancer Database (NCDB) for pACC was used. Cox regression was used in resected pACC patients to identify significant overall survival (OS) predictors. Patients were then divided based on these risk factors into propensity-matched group of surgery versus surgery + chemotherapy and Kaplan-Meier analysis was performed with log-rank tests to compare OS. The NCDB 2004-2020 included 1592 pACC patients, 1553 were selected. Median age was 66 and 1090 (70.2%) were males. 622 (40.1%) received chemotherapy only, 257 (16.5%) had surgery only, and 365 (23.5%) had both. 189 Patients who received surgery were only matched to peers who had surgery + chemotherapy. The median OS for surgery only was 57.8 ± 6.0 versus 54.2 ± 9.9 months for surgery + chemotherapy (p = 0.836). Cox regression identified nodal and margin status as independent predictors of OS. Therefore, subgroups of patients with node-negative, node-positive, margin-negative, and margin-positive resections were similarly matched 1:1 for the receipt of surgery only versus surgery + chemotherapy. Only patients with node-positive disease had a significant OS benefit with the addition of chemotherapy (44.2 ± 7.3 vs. 27.5 ± 10.5 months; p = 0.036). Our analysis suggests that surgical resection remains the cornerstone of therapy for pACC. Node status and margin status are the primary prognosticators. The addition of chemotherapy provides an OS benefit only in node-positive disease.

Elevated serum direct bilirubin is predictive of a poor prognosis for primary myelodysplastic syndrome.

The aim of this study was to assess the prognostic significance of serum direct bilirubin (DBIL) for patients newly diagnosed with myelodysplastic syndromes (MDS). The clinical, laboratory, and follow-up data of MDS patients were collected, and the associations of DBIL levels with overall survival (OS) and leukemia-free survival (LFS) were analyzed. In total, 262 MDS patients were assigned to the high DBIL level group or the normal DBIL level group in the retrospective study. High DBIL was associated with older age, reduced hemoglobin, higher levels of β2-microglobin, lactate dehydrogenase, and serum ferritin, along with the number of co-mutations (> 1) and a higher frequency of ASXL1, KIT, and KRAS mutations. Multivariate analyses found that high DBIL level was an independent adverse predictor for OS (p = 0.002, hazard ratio = 2.723, 95%CI = 1.442-5.143) but not for LFS (p = 0.057, hazard ratio = 1.678, 95%CI = 0.986-2.857). A novel nomogram based on DBIL, sex, age, β2-microglobulin, lactate dehydrogenase, the Revised International Prognostic Scoring System (IPSS-R) was constructed, which demonstrated superior accuracy compared with the IPSS-R (C-index, 0.790 vs. 0.731, respectively). An elevated DBIL level was identified as an independent adverse prognostic factor for MDS patients. An individualized prediction model was established and validated to improve prediction of OS and LFS.

NIMG-72. VOXEL-WISE, MULTIVARIABLE, COX PROPORTIONAL HAZARD STATISTICAL PARAMETER MAPPING TO INVESTIGATE THE INTERPLAY BETWEEN TUMOR LOCATION, PROGNOSTIC VARIABLES, AND EXPERIMENTAL TREATMENT IN A PHASE 3 TRIAL OF NEWLY-DIAGNOSED GLIOBLASTOMA TREATED WITH CHEMORADIATION WITH OR WITHOUT BEVACIZUMAB

Abstract BACKGROUND Tumor location is known to impact overall survival (OS) in glioblastoma. However, there is a lack of quantitative tools for studying the interplay between tumor location, prognostic variables, and treatments. In the current study we develop a voxel-wise statistical parameter mapping technique using a multivariable Cox regression model to describe the influence of tumor location on treatment effects in newly diagnosed glioblastoma. METHODS 598 newly diagnosed glioblastoma patients from the phase 3 AVAglio trial were studied. Areas of T2/FLAIR hyperintensity and resection cavities on post-surgical MRI scans were segmented and aligned to MNI atlas space. Voxel-wise Cox proportional hazards models for OS were run for each image voxel and included tumor presence in a specific voxel, age, MGMT promoter methylation, baseline tumor volume, and treatment (chemoradiation with or without bevacizumab). Results. After adjusting for other variables, tumor location was an independent predictor of favorable OS for tumors with involvement in the right prefrontal cortex (p&amp;lt;0.05, HR ranging ~0.48–0.65) and a predictor of shorter OS for tumors in the left mesial/basal temporo-occipital areas (p&amp;lt;0.05, HR ~3–6.2) and in the left hemisplenium of the corpus callosum (p&amp;lt;0.05, HR ~2.5–3). Baseline tumor volume (HR ~4–6 x10-6), MGMT status (HR ~0.38–0.41), and age (HR ~1.020–1.025) were significative predictors regardless of location (p&amp;lt;0.05 in all locations). Interestingly, chemoradiation plus bevacizumab treatment showed a favorable OS compared with chemoradiation alone for tumors with involvement in the right corticospinal tract, right motor and sensory cortices, and left hemisplenium of the corpus callosum (p&amp;lt;0.05, HR ~0.82). CONCLUSIONS Tumor involvement in the prefrontal cortex is associated with favorable prognosis, while tumors in mesial/basal temporo-occipital areas or splenium of the corpus callosum are associated with shorter OS. Chemoradiation plus bevacizumab may improve OS for tumors involving eloquent motor areas and the corticospinal tract.

NIMG-75. SIMILARITY DISTANCES-BASED DELTA RADIOMICS (SDDR) ENABLES LONGITUDINAL MRI COMPARISONS FOR SURVIVAL PREDICTION IN GLIOMAS: A MULTI-INSTITUTIONAL VALIDATION

Abstract Radiomics (computerized feature analysis) on treatment-naive MRI scans has demonstrated great value in outcome prediction for Glioblastoma (GBM). However, delta radiomics (analysis of radiomic feature variation between different events, e.g., before and after treatment) has not been explored on account of challenges with precise spatial correspondences between pre- and post-operative scans. This work presents a survival prediction model for GBM, Similarity Distances-based delta radiomics (SDDR), based on the hypothesis that similarity distance-measures between radiomic features on pre-, and post-treatment images can accurately capture temporal changes within-and-around the tumor, and provide improved prediction of overall survival, compared to models based on a single timepoint. 150 patients from 2 publicly-available Glioma repositories (University of California San Francisco “UCSF” (n=48), LUMIERE (n=67)) and 2 two proprietary datasets (from xCures (n=13), and Cleveland Clinic (CCF) (n=74)) were obtained. UCSF and LUMIERE cohorts were used as separate hold-out sets, in each of which the remaining collections were used as discovery set. Following pre-processing, tumor segmentation into Edema (ED) and Enhancing tumor (ET) were performed. SDDR was then computed, which is the distance between probability densities functions from 156 gray co-occurrence (GLCM) and 52 gradient-based co-occurrences statistics (COLLAGE) features extracted from pre and-post-treatment MRI. Six statistical distances (e.g., Earth mover distance) normalized by the scanning interval (in weeks) yielded n=2496 SDDR measurements per tumor region (1248/region, 936 delta-GLCM, and 312 delta-COLLAGE). The same set of features were computed from pretreatment MRI (Pre-R) for comparison. Features were fed to LASSO-Cox regression for survival analysis. SDDR for GLCM features extracted from ET outperformed Pre-R, and demonstrated significant differences between high and low risk groups for both hold out tests: UCSF (p=0.0069, HR =2.8, C-index=0.69) and LUMIERE (p=0.0061, HR = 1.9, C-index 0.65). SDDR-based multi-institutional survival analysis demonstrated promise in reliable longitudinal risk-stratification in GBM.