Prognostic Factor For Survival Outcome Research Articles

Real-world clinical outcomes and prognostic factors of olaparib maintenance in Korean patients with primary or recurrent high-grade ovarian cancer with exploratory analysis of location of BRCA1 and BRCA2 mutations.

e17561 Background: Olaparib is approved for first-line (1L) and second or subsequent-line (2L+) maintenance therapy in BRCA-mutated ovarian cancer (OC). However, the correlation between location of BRCA mutation and benefit of olaparib maintenance therapy has not been thoroughly investigated. We aimed to analyze real-world clinical outcomes and identify prognostic factors for olaparib maintenance therapy in Korean patients with BRCA-mutated OC, focusing on BRCA mutation sites. Methods: This retrospective cohort study included Korean patients with BRCA-mutated OC who received olaparib as 1L or 2L+ at the single center between January 2015 and April 2023. Survival outcomes and toxicity were correlated with BRCA mutation location summaries and patient characteristics by maintenance therapy line. Results: For the 1L group (n = 70), 2-year PFS and 3-year OS were 75.5% (95% CI, 56.4–87.1) and 98.5% (95% CI, 90.0–99.8). For the 2L+ group (n = 83), 2-year PFS and 3-year OS were 54.8% (95% CI, 56.4–87.1) and 87.3% (95% CI, 76.7–93.3). Primary stage (IV vs. ≤ III) was a prognostic factor for PFS in the 1L group (adjusted hazard ratio [aHR], 5.74; 95% CI, 1.23–26.73; P = 0.026). Notably, Korean-specific pathogenic variant p.Leu1780Pro BRCA1 mutation carriers (n= 8) showed significantly worse PFS than non-carriers (n = 32) in the 1L group (Log-rank P = 0.014). For the 2L+ group, platinum-free interval ≥ 12 months was a good prognostic factor for both PFS (aHR, 0.42; 95% CI, 0.23–0.75) and OS (aHR, 0.31; 95% CI, 0.11–0.91). Additionally, somatic BRCA1 mutation was a poor prognostic factor for PFS in the 2L+ group (hazard ratio [HR], 3.39; 95% CI, 1.22–9.38; P = 0.029). In the 1L group, the longer interval between the last chemotherapy and maintenance therapy was associated with the lower risk of hematologic toxicity induced by olaparib (odd ratio [OR], 0.75; 95% CI 0.57–0.99; P = 0.04). In addition, age ≥ 65 years (OR, 3.33; 95% CI, 1.05–10.63; P = 0.04) and the dose reduction of the last chemotherapy (OR, 3.80; 95% CI, 1.02–14.18; P = 0.047) were associated with a higher risk of hematologic toxicity in the 1L group. In the 2L+ group, germline BRCA1 (OR, 0.36; 95% CI, 0.14–0.92; P = 0.03) and BRCA2 (OR, 7.47; 95% CI, 1.96–28.39; P = 0.003) mutations showed contrariwise risks for hematologic toxicity. Drug discontinuation due to toxicity was 1.4% and 6.0% in the 1L and the 2L+ groups and no acute myeloid leukemia/myelodysplastic syndrome cases were observed. Conclusions: Olaparib maintenance therapy was effective and tolerable in Korean patients with BRCA-mutated OC. Prognostic factors for survival outcomes and risk factors of hematologic toxicity in olaparib maintenance therapy were different between 1L and 2L+. The prognostic significance of Korean-specific p.Leu1780Pro BRCA1 mutation on olaparib should be further researched.

Sex-specific Differences in IDH1-Wildtype Glioblastoma patients in the ReSPOND Consortium.

Understanding sex-based differences in glioblastoma patients is necessary for accurate personalized treatment planning to improve patient outcomes. To investigate sex-specific differences in molecular, clinical and radiological tumor parameters, as well as survival outcomes in glioblastoma, isocitrate dehydrogenase-1 wildtype (IDH1-WT), grade 4 patients. Retrospective data of 1832 glioblastoma, IDH1-WT patients with comprehensive information on tumor parameters was acquired from the Radiomics Signatures for Precision Oncology in Glioblastoma (ReSPOND) consortium. Data imputation was performed for missing values. Sex-based differences in tumor parameters, such as, age, molecular parameters, pre-operative KPS score, tumor volumes, epicenter and laterality were assessed through non-parametric tests. Spatial atlases were generated using pre-operative MRI maps to visualize tumor characteristics. Survival time analysis was performed through log-rank tests and Cox proportional hazard analyses. GBM was diagnosed at a median age of 64 years in females compared to 61.9 years in males (FDR = 0.003). Males had a higher Karnofsky Performance Score (above 80) as compared to females (60.4% females Vs 69.7% males, FDR = 0.044). Females had lower tumor volumes in enhancing (16.7 cm3 Vs. 20.6 cm3 in males, FDR = 0.001), necrotic core (6.18 cm3 Vs. 7.76 cm3 in males, FDR = 0.001) and edema regions (46.9 cm3 Vs. 59.2 cm3 in males, FDR = 0.0001). Right temporal region was the most common tumor epicenter in the overall population. Right as well as left temporal lobes were more frequently involved in males. There were no significant differences in survival outcomes and mortality ratios. Higher age, unmethylated O6-methylguanine-DNAmethyltransferase (MGMT) promoter and undergoing subtotal resection increased the mortality risk in both males and females. Our study demonstrates significant sex-based differences in clinical and radiological tumor parameters of glioblastoma, IDH1-WT, grade 4 patients. Sex is not an independent prognostic factor for survival outcomes and the tumor parameters influencing patient outcomes are identical for males and females. IDH1-WT = isocitrate dehydrogenase-1 wildtype; MGMTp = O6-methylguanine-DNA-methyltransferase promoter; KPS = Karnofsky performance score; EOR = extent of resection; WHO = world health organization; FDR = false discovery rate.

Abstract 7644: Prognostication of genomic characteristics of residual breast cancer after neoadjuvant chemotherapy

Abstract Residual cancer burden (RCB) based on pathologic characteristics is the most powerful prognostic factor in breast cancer (BC) which received neoadjuvant chemotherapy (NAC) followed by surgery. According to RCB classification, class III predicted short survival duration regardless of BC subtypes according to hormone receptor (HR) and human epidermal growth factor receptor-2 (HER-2) state. However, up to 20-40% of BCs with RCB class III did not experience BC recurrence and had long term survival without disease recurrence. In our study, we evaluated genomic characteristics of BC which had high RCB class. We collected 96 fresh frozen BC specimens which had undergone surgery after NAC between 2010 and 2018 from Samsung Medical Center Biobank. We performed whole genome or exome sequencing, RNA sequencing and high-plex single-cell spatial transcriptomics. Of 96 BCs, 65 BCs had experienced BC recurrence and 31 BCs have not been BC recurrence. Of 65 BCs with dismal prognosis, 12 were HR+HER2-, four in HR+HER2+, 39 in triple negative breast cancer (TNBC) and 10 in HR-HER2+ BC. Of 31 BCs without recurrence, 11 were HR+HER2-, two in HR+HER2+, 14 in TNBC and four in HR-HER2+ BC. In HR+HER2- BC, ten of 12 BCs with dismal prognosis were categorized into basal like intrinsic subtype and two were into luminal B subtype compared that six of luminal A and five of luminal B subtype categorization in good prognosis BC group. Age associated mutation signature were enriched in HR+HER2- BC with good prognosis (p=0.027). Tumor microenvironment (TME) analysis using Kassandra suggested that high monocytes were associated with BC with dismal prognosis (p=0.00031). In single-cell spatial transcriptome analysis, T-cell abundance in the tumoral niche is associated with dismal prognosis in HR+HER2- BC (p=0.039). In TNBC, almost BCs (88.7%) were categorized into basal-like intrinsic subtype regardless of their prognosis. TME analysis presented that immune cells including macrophages and lymphocytes with CD4 and CD8 T cells were significantly enriched in TNBC with good prognosis (ps <0.05, respectively). In HER2+ BC, intrinsic subtypes were heterogeneous in both groups. Focal amplification in HER2+BC patient harbored DNA segments from different chromosomes more frequently than in those with good prognosis (p=0.00091), which was prominent in oncogenic extrachromosomal DNA amplifications compared to other oncogenic amplifications. In TME analysis, there were no specific cell enrichments according to BC prognosis but sing-cell spatial transcriptome analysis revealed that higher T-cell abundance in the tumoral niche was associated with HR+HER2+ BC with good prognosis (p=0.047). In conclusion, each BC subtype had their own genomic characteristics to determine their prognosis. Our study also suggested that TME characteristics was common prognostic factor for survival outcome of BC with residual tumor after NAC. Citation Format: Ji-Yeon Kim, Sabin Park, Sepil Ahn, Eun Seop Seo, Soyeon Kim, Mark Gregory, Emily Killingbeck, Eun Yoon Cho, Jeong Eon Lee, Jin Seok Ahn, Yeon Hee Park, Woong-Yang Park, Hoon Kim, Semin Lee, Young-Hyuck Im. Prognostication of genomic characteristics of residual breast cancer after neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7644.

Treatment Outcomes of Olfactory Neuroblastoma: A Multicenter Study by the Korean Sinonasal Tumor and Skull Base Surgery Study Group.

Due to the rarity of olfactory neuroblastoma (ONB), there is ongoing debate about optimal treatment strategies, especially for early-stage or locally advanced cases. Therefore, our study aimed to explore experiences from multiple centers to identify factors that influence the oncological outcomes of ONB. We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and a Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. In our cohort, the 5-year overall survival (OS) rate was 78.6%, and the 5-year disease-free survival (DFS) rate was 62.4%. The Cox proportional hazards model revealed that the modified Kadish (mKadish) stage and Dulguerov T status were significantly associated with DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though the result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Similarly, induction chemotherapy also did not show a survival benefit, even after stage matching.

Handling missing covariates in observational studies: an illustration with the assessment of prognostic factors of survival outcomes in soft-tissue or visceral sarcomas in irradiated fields (SIF).

Missing covariates are common in observational research and can lead to bias and loss of statistical power. Limited data regarding prognostic factors of survival outcomes of sarcomas in irradiated fields (SIF) are available. Because of the long lag time between irradiation of first cancer and scarcity of SIF, missing data are a critical issue when analyzing long-term outcomes. We assessed prognostic factors of overall (OS), progression-free (PFS), and metastatic-progression-free (MPFS) survivals in SIF using three methods to account for missing covariates. We relied on the NETSARC French Sarcoma Group database, Cox (OS/PFS), and competitive hazards (MPFS) survival models. Covariates investigated were age, sex, histological subtype, tumor size, depth and grade, metastasis, surgery, surgical resection, surgeon's expertise, imaging, and neo-adjuvant treatment. We first applied multiple imputation (MI): observed data were used to estimate the missing covariate. With the missing-data modality approach, a category missing was created for qualitative variables. With the complete-case (CC) approach, analysis was restricted to patients without missing covariates. CC subjects (N = 167; 33%) presented more often with soft-tissue sarcoma (versus visceral sarcoma) and grade I-II tumors as compared to the 504 eligible cases. With MI (N = 504), factors associated with the worst outcome included metastasis (p = 0.04) and R1/R2 resection (p < 0.001) for OS; higher grade/non-gradable tumors (p = 0.002) and R1/R2 resection (p < 0.001) for PFS; and metastasis (p = 0.01) for M-PFS. The 'missing-data modality' approach (N = 504) led to different associations, including significance reached due to variables with the modality 'missing'. The CC analysis led to different results and reduced precision. The CC population was not representative of the eligible population, introducing bias, in addition to worst precision. The 'missing-data modality method' results in biased estimates in non-randomized studies, as outcomes may be related to variables with missing values. Appropriate statistical methods for missing covariates, for example, MI, should therefore be considered.

Prognostic Value of The Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Platelet Count for Platinum-Sensitive Recurrent Epithelial Ovarian Cancer.

To study the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and platelet count in patients with platinum-sensitive recurrent epithelial ovarian cancer (PS-ROC). This was a retrospective study on a database of platinum-sensitive recurrent epithelial ovarian cancer patients who received treatment at HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) between January 2010 and December 2020. The patients' demographic data, surgical factors, pathological factors, laboratory findings, and response to treatment were reviewed from the patients' medical records. Survival analysis was conducted using the Kaplan-Meier survival estimate and Cox regression model. In total, 56 patients were recruited in this study. The median overall survival (OS) and progression-free survival (PFS) were 33 (95%CI 23-43) and 11 (95%CI 8-16) months, respectively. Survival analysis showed a high PLR was associated with decreased OS compared with low value but no significant difference in PFS. High NLR was associated with poor OS and PFS. There was no association between the platelet count and survival outcome (OS and PFS). In the multivariable Cox regression analysis, the NLR, PLR, and platelet count were not significant prognostic factors for survival outcome. However, low hemoglobin and a decreased disease-free interval were significantly associated with poor PFS. A white blood cell count (WBC) ≥ 8,000 cells/mm3 was a poor prognostic factor for overall survival (Adjusted HR 7.64; 95%CI: 2.21-26.42; p-value = 0.001). The NLR, PLR, and platelet count were not associated with both the OS or PFS in patients with PS-ROC. However, the WBC level is an easy, readily available, and economical way to predict survival outcomes in PS-ROC patients and may help physicians to tailor therapeutic interventions in the future.

Exploring the Clinical Characteristics and Survival of Early-Onset and Late-Onset Nasopharyngeal Carcinoma

Presently, early-onset and late-onset nasopharyngeal cancer (EONPC and LONPC, defined as age ≤ 50 years and > 50 years old, respectively) are seldom studied. The purpose of this study is to determine the clinical and survival characteristics between the NPC patients of these two age groups. Patients diagnosed with NPC in The Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2018 years, and in our institution from 2014 to 2017 years were reviewed in this study. Clinicopathological characteristics, treatment modalities, and survival outcomes of EONPC and LONPC patients were analyzed and compared. A total of 2943 patients (including 935 patients with EONPC and 2008 patients with LONPC) in the SEER database and 833 domestic patients (including 518 patients with EONPC and 315 patients with LONPC) in our center were finally enrolled. In the SEER database, both EONPC and LONPC patients displayed a greater prevalence in men. EONPC patients presented with a worse staging of regional lymph node metastasis (p < 0.001), but had a better prognosis than that in the LONPC patients (p < 0.001). More EONPC patients received chemotherapy and radiation (p < 0.001). Similar results were validated in our center, and in addition, it was found that EONPC patients had an advanced clinical stage (stage III, IVA, 92.1% vs. 85.1%, p = 0.016) and larger primary tumor volume (41.7% vs. 35.7%, p = 0.049). Meanwhile, EONPC patients had a superior overall survival (OS) (p = 0.017) and cancer-specific survival (CSS) (p = 0.004) compared to that in the LONPC patients. In univariate and multivariate Cox regression analysis, early-onset was independently associated with a higher 5-year OS (82.4% vs. 73.3%, p = 0.006). EONPC patients present with more advanced lymph node metastasis stage and clinical stage, but have a better survival compared to LONPC patients. Age ≤ 50 years was an independent prognostic factor for survival outcome in NPC patients. To achieved the better individualization of the therapeutic regimen, there is the need for further studies on EONPC.

JS07.5.A PROGNOSTIC FACTORS ASSOCIATED WITH POOR OUTCOME IN ADULT PATIENTS WITH MEDULLOBLASTOMA

Abstract BACKGROUND Medulloblastoma (MB) is a rare tumor in adults. Current recommendations are based on scarce data available in adults, and mostly derived from pediatric series. Prognostic factors have not been uniformly defined in adults to date. MATERIAL AND METHODS We retrospectively collected all cases of adult patients diagnosed and treated between 1995 and 2019 in our institution for histopathological proven MB. We described patient´s characteristics, disease features, treatment modalities and studied the prognostic factors for survival outcomes using univariate and multivariate analysis. RESULTS We identified a total of 89 cases. Male gender (66%), lateral cerebellar location (48%), desmoplastic/nodular histology (43%), Sonic Hedgehog molecular group (76%) and Chang´s M0 (72%) were the most frequent patient´s and disease characteristics. Patients mostly achieved complete resection/near total resection (62%); surgery followed by chemotherapy/radiotherapy (CT/RT) was the most frequent initial strategy (76%), favoring carboplatin-based regimens (70%), posterior fossa RT ≥50 Gy (71%) and craniospinal RT ≥ 30 Gy (59%) as the most frequently regimen used. According to the Association of French Speaking Neuro-oncologists and the European Reference Network on Rare Adult Cancers risk scales (ANOCEF and EURACAN), we found 44 and 48% of intermediate-risk patients and 49 and 45% of high-risk patients, respectively. Both cerebral and spinal presentation at diagnosis was documented in 16 (18%) patients. Complete response was achieved in 71(80%) patients. Nine was the maximal number of progressions documented, 35(39%) patients relapsed, CT was the preferred strategy at relapses, privileging carboplatin-based regimens at first relapse. The median overall survival (mOS) was 124.42 months (95%CI 68.53 - 180.11) and the median progression free survival (mPFS) was 30.48 months (95%CI 13.46 - 47.51), the 5-year OS was 53% and the 5-year PFS was 51%. In multivariate analysis, Chang´s ≥ M2 metastatic classification (p=0.001), no CT in association to RT (p=0.005), and lower doses on craniospinal RT &amp;lt;30 Gy (p=0.015) were associated with poor prognosis for OS; Chang´s ≥ M2 (p=0.009) was also a prognostic factor for poor PFS. CONCLUSION This study dedicated specifically to adult MB patients suggests relevant prognostic factors for adult MB patients. We identify Chang´s ≥ M2 as poor prognostic factor of OS and PFS, and we confirm that the use of CT/RT at diagnosis and RT doses ≥ 30 Gy are associated with better survival in adults MB.

Modified staging system of positive lymph nodes based nomogram in intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (iCCA) presents the similar trend and prevalence of lymph node metastasis to other biliary tract cancer. There is still a necessity and possibility for the current classification of lymph node in the 8th TNM of iCCA, which is the same as the criteria of hepatoma carcinoma (HCC), to further improve the prognostic capacity. We aim to explore the optimal positive lymph nodes cutoff value that could predict the survival outcomes of patients with iCCA and further establish a prognostic nomogram.MethodClinical characteristics were retrospectively collected in 292 patients with iCCA from Sun Yat-sen University Cancer Center (SYSUCC) for preliminary analysis. A retrospective analysis of 107 patients with iCCA in the First Hospital of Dalian Medical University (FHDMU) was performed for verification. R software was used to determine the optimal cutoff value of positive lymph nodes (PLN) and further establish the nomogram with the Cox regression model in the primary cohort.ResultsIn those patients who were graded into the N1 stage in 8th TNM staging system, the patients with PLN between 1 and 3 showed significantly better overall survival than those patients with more than 4 PLN (P < 0.0001). Moreover, there was a significant correlation between the new PLN classification and adverse clinical characteristic including Micro Invasion (P = 0.001), Lymph Vessel Invasion (P = 0.040), Satellite Sites (P < 0.001), and Tumor Size (P = 0.005). The PLN and ELN were both independent prognostic factors for survival outcomes in the multivariate analysis, and further showed large contribution to the nomogram. The nomogram achieved a satisfied C-index of 0.813 for overall survival (OS), 0.869 for progression-free survival (PFS) in the primary cohort, and 0.787 for OS, 0.762 for PFS in the validation cohort.ConclusionThe modified classification of PLN in iCCA could accurately stratify the N1 stage patients in 8th TNM staging system into two groups with significantly different overall survival. The development of this nomogram can offer new evidence to precisely post-operative management of iCCA patients.

Persistent high levels of carcinoembryonic antigen after tumor resection are associated with poorer survival outcomes in patients with resected colon cancer

BackgroundInterindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent.MethodsWe conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico’s National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS).ResultsWe included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9–147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6–71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6–81.6). Group B: 75.7 months (95% CI 66.8–84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8–76.3) months] than in group A [82.8 (95% CI 78.6–86.9 months] and group B [87.1 (95% CI 79.6–94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031).ConclusionsWhen assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.

Metastatic breast cancer in Kenya: survival, prognosis and management at a tertiary referral centre.

There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with advanced disease. However, there is little data on survival outcomes and prognostic factors affecting survival in patients with metastatic breast cancer (MBC) in Africa. The study objective was to establish the survival of patients with MBC at a single tertiary health facility, the clinical and pathological characteristics affecting survival and describe the treatment modalities used. This was a retrospective descriptive study conducted at Aga Khan University Hospital, Nairobi of patients diagnosed with MBC between 2009 and 2017. Survival data was collected on metastatic free survival, survival time between diagnosis of first metastasis and death and overall survival. Data on patient's age, menopausal status and stage at diagnosis, tumour grade, receptor status, site of metastasis and treatment given was also collected. The Kaplan-Meier Estimator was used to estimate survival. Prognostic factors for survival outcomes were analysed using univariate analysis. Standard descriptive statistics were used to describe patient characteristics. A total of 131 patients were included in the study. The median survival was 22 months. The 3 and 5-year survivals were 31.3% and 10.7%, respectively. On univariate analysis, the Luminal A molecular subtype was a significant positive prognostic factor hazard ratios (HR 0.652 95% confidence interval (CI) 0.473-0.899) while metastasis to the liver or brain were significant negative prognostic factors (HR 0.615 95% CI 0.413-0.915 and HR 0.566 95% CI 0.330-0.973, respectively). A large proportion (87.0%) received some treatment for metastatic disease. Our study concluded that survival rates for patients diagnosed with MBC were lower compared to studies from Western countries but higher than in studies from Sub-Saharan Africa. Luminal A molecular subtype was found to be a positive prognostic factor and metastasis to the liver or brain were found to be negative prognostic factors. Improved access to adequate treatment for MBC is required in the region.

Favorable prognostic factors for survival outcomes of hepatocellular carcinoma with portal vein tumor thrombosis after hepatectomy

Favorable prognostic factors for survival outcomes of hepatocellular carcinoma with portal vein tumor thrombosis after hepatectomy

Less Irradiation to Lymphocyte-Related Organs Reduced the Risk of G4 Lymphopenia in Esophageal Cancer: Re-Analysis of Prospective Trials.

This study aimed to explore the relationship between irradiation of lymphocyte-related organs at risk (LOARs) and lymphopenia during definitive concurrent chemoradiotherapy (dCCRT) for esophageal squamous cell carcinoma (ESCC). Cases of ESCC patients who received dCCRT from 2 prospective clinical trials were identified. To find its correlation with survival outcomes, grades of absolute lymphocyte counts (ALCs) nadir during radiotherapy were recorded following COX analysis. Associations of lymphocytes at nadir and dosimetric parameters including relative volumes of spleen and bone marrow receiving 0.5, 1, 2, 3, 5, 10, 20, 30, and 50Gy (V0.5, V1, V2, V3, V5, V10, V20, V30, and V50), and effective dose to circulating immune cells (EDIC) were examined by logistic risk regression analysis. The cutoffs of dosimetric parameters were determined by the receiver operating characteristic curve (ROC). A total of 556 patients were included. The incidences of grades 0, 1, 2, 3, and 4 (G4) lymphopenia during dCCRT were 0.2%, 0.5%, 9.7%, 59.7%, and 29.8%, respectively. Their median overall survival (OS) and progression-free survival (PFS) time were 50.2 and 24.3 months, respectively; the incidence of local recurrence and distant metastasis were 36.6% and 31.8%, respectively. Patients once suffering from G4 nadir during radiotherapy had unfavorable OS (HR, 1.28; P = .044) and a higher incidence of distant metastasis (HR, 1.52; P = .013). Furthermore, patients with EDIC ≤8.3Gy plus spleen V0.5 ≤11.1% and bone marrow V10 ≤33.2% were strongly associated with lower risk of G4 nadir (OR, 0.41; P = .004), better OS (HR, 0.71; P = .011) and lower risk of distant metastasis (HR, 0.56; P = .002). Smaller relative volumes of spleen V0.5 and bone marrow V10 plus lower EDIC were jointly prone to reduce the incidence of G4 nadir during definitive concurrent chemoradiotherapy. This modified therapeutic strategy could be a significant prognostic factor for survival outcomes in ESCC.

Integrated single-cell and bulk characterization of cuproptosis key regulator PDHB and association with tumor microenvironment infiltration in clear cell renal cell carcinoma.

Renal clear cell carcinoma (ccRCC) is one of the most prevalent cancers worldwide. Accumulating evidence revealed that copper-induced cell death played a vital role in various tumors. However, the underlying mechanism of cuproptosis with molecular heterogeneity and tumor microenvironment (TME) in ccRCC remains to be elucidated. The present study aimed to discover the biological function of cuproptosis regulators with the potential to guide clinical therapy. Using Single-cell RNA-seq, bulk transcriptome and other multi-omics datasets, we identify essential cuproptosis-related hub gene PDHB for further study. The dysregulation of PDHB in ccRCC was characterized, together with survival outcomes, pathway enrichment and immune infiltration among tumor microenvironments. The functional significance and clinical association of PDHB was validated with loss of function experiments and surgical removal specimens. PDHB mRNA and protein expression level was significantly downregulated in ccRCC tissues compared with normal and paired normal tissues. Clinicopathological parameters and tissue microarray (TMA) indicated that PDHB was identified as a prognostic factor for survival outcomes among ccRCC patients. Additionally, low PDHB was negatively correlated with Treg cells, indicating an immunosuppressive microenvironment. Mechanistically, knockdown PDHB appeared to promote the RCC cells proliferation, migration, and invasion potentials. Subsequent studies showed that copper-induced cell death activation could overcome sunitinib resistance in RCC cells. This research illustrated a cuproptosis-related hub gene PDHB which could serve as a potential prognostic marker and provide therapeutic benefits for clinical treatment of ccRCC patients.

Complete response in the axilla and the non-triple negative subtype are favourable prognostic factors for survival outcomes in inflammatory breast cancer.

To assess real-world outcomes and prognostic factors of non-metastatic inflammatory breast cancer according to immunohistochemistry (IHC)-based subtype and treatment regimen. An institutional retrospective analysis of patients treated with neoadjuvant systemic treatment (NAST) for stage III inflammatory breast cancer diagnosed between 2001 and 2018 was performed. The survival outcomes in relation to patient characteristics, tumour characteristics, treatment modality and response to NAST were analyzed. 225 patients fulfilled the inclusion criteria, 90% of patients were node-positive. IHC-based subtypes: 39.1% were HR+/HER2-, 19.1% HR+/HER2+, 23.1% HR-/HER2+ and 18.7% HR-/HER2-. Treatment was multimodal: NAST (100%), surgery (94.2%) and radiotherapy (94.2%). 53.3% of patients received adjuvant endocrine therapy, 34.3% (neo)adjuvant trastuzumab. Tri-modality therapy was applied in 89.3% of patients. Following NAST, a pathologic complete remission (pCR) in the breast was found in 16.9%, in the axilla in 29.7% and in both the breast and axilla in 10.3% of patients. The axillary pCR rate was significantly higher in HR- subtypes. Median overall survival (OS) was 8.9, 7.2, 5.8 and 2.3 years (p<0.001) for HR+/HER2-, HR+/HER2+, HR-/HER2+ and HR-/HER2- subtype, respectively. On multivariate analysis, IHC-based subtype, age and axillary pCR were found as independent prognostic factors for RFS and OS. pCR rate and median OS improved over time, 5.8% vs 14.7% and 4.7 vs 10.0 years (2001-2009 vs. 2010-2018), respectively. Axillary pCR and the non-triple-negative IHC-based subtype are favourable prognostic factors for RFS and OS in inflammatory breast cancer. Introduction of taxanes and antiHER2 drugs contributed to improved pCR rate and OS.

Validation of the ALBI-TAE model and comparison of seven scoring systems for predicting survival outcome in patients with intermediate‐stage hepatocellular carcinoma undergoing chemoembolization

BackgroundThe ALBI-TAE model was recently proposed as a scoring system to select suitable patients with intermediate-stage hepatocellular carcinoma (HCC) for transarterial chemoembolization (TACE). However, this scoring system has not been externally validated. Therefore, we validated this score and compared it with six scoring systems in terms of prognostication.MethodsWe retrospectively enrolled 480 patients with intermediate-stage HCC who underwent TACE at a tertiary care center between January 2008 and December 2019. Seven scores, which included the ALBI-TAE model, Bolondi’s subclassification, HAP score, mHAP-II score, tumor burden score, six-and-twelve score, and seven-eleven criteria, were calculated and a head-to-head comparison was made in terms of prognostic power using Harrell’s C-index. Prognostic factors associated with survival were analyzed.ResultsALBI-TAE group A had the longest median overall survival (OS) of 40.80 months, followed by ALBI-TAE groups B, C, and D of 20.14 months, 10.58 months, and 7.54 months, respectively, with significant differences (P < 0.001). Among the seven scores, the ALBI-TAE model had the best predictive performance (Harrell’s C-index 0.633) in differentiating OS in intermediate-stage HCC patients. Moreover, the ALBI-TAE model was identified as an independent prognostic factor for survival outcome in multivariate analysis.ConclusionOur study confirmed the value of the ALBI-TAE model with excellent prognostic discriminatory power in intermediate-stage HCC patients. The ALBI-TAE model is a simple and valuable predictive tool to identify patients with good prognosis who can get the most benefit from TACE.

Favorable Prognostic Factors for Survival Outcomes of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis After Hepatectomy.

This study aimed to investigate prognostic factors of recurrence and survival associated with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). This retrospective study included 161 patients with HCC with PVTT who underwent hepatectomy between January 2003 and January 2014 at the Asan Medical Center. Regression analyses were conducted to identify favorable predictive factors for overall survival (OS) and recurrence-free survival (RFS). The median follow-up was 15.9 months, while 1-, 3-, and 5-year OS was 65.0%, 38.4%, and 36.0%, respectively, and 1-year RFS was 25.5%. There were no significant differences in OS and RFS between the patients with portal vein invasion (Vp) 1-2 and Vp3-4 PVTT. Patients with intrahepatic recurrence had significantly better overall survival than patients with extrahepatic recurrence. Transcatheter arterial chemoembolization and radiofrequency ablation were the most effective treatments for intrahepatic metastasis, and surgery was the most effective treatment for extrahepatic metastasis. On multivariate analysis, absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection were favorable prognostic factors for OS and R0 resection, and absence of microvascular invasion was a favorable prognostic factor for RFS. The long-term outcome of patients with HCC with PVTT can be improved under consideration of favorable prognostic factors including absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection, R0 resection, and absence of microvascular invasion. In addition, recurrent HCC required aggressive management to prolong overall survival.

Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study

BackgroundThe prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC.MethodsData made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse.ResultsThe median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 − 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 − 3.81]).ConclusionAfter adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

Adequate lymph node dissection is essential for accurate nodal staging in intrahepatic cholangiocarcinoma: A population-based study.

To comprehensively investigate the implications of lymph node dissection (LND) and the prognostic impact of the number of lymph node (LN) metastases on survival in intrahepatic cholangiocarcinoma (ICC) using a large-scale study. Patients who underwent surgical resection for ICC between 2004 and 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) registries. The Kaplan-Meier and log-rank tests were used to compare cancer-specific survival (CSS) and overall survival (OS) between different groups. Propensity score matching (PSM) and subgroup analyses were performed to balance potential confounding factors. A multivariate Cox proportional hazards regression model was used to identify prognostic factors of survival outcomes. Restricted cubic splines fitted in the Cox proportional hazard regression models were also conducted to examine associations between continuous variables and outcomes. In all, 1028 patients were enrolled. There were 652 (63.4%) patients undergoing LND, with lymph node metastasis (LNM) confirmed in 212 (32.5%) cases. Patients receiving LND did not show better survival outcomes than those receiving non-LND (NLND). We divided the LND group into two subgroups: patients with LNM (+) and those without LNM (-). Among these three groups, patients with LNM experienced the worst CSS and OS, while NLND patients had similar survival times to LNM (-) patients. Restricted cubic spline analysis indicated that an increased number of LNM was associated with a decreased chance of survival (p < 0.001). Patients who received LND were further categorized as having no nodal metastasis (N0), 1-2 LNM (N1), or ≥3 LNM (N2) according to the number of LNM. The Kaplan-Meier curves showed that the mortality risk of patients with N0, N1, and N2 disease (median CSS, N0 50.0 vs. N1 22.0 vs. N2 14.0months; median OS, N0 46.0 vs. N1 21.0 vs. N2 14.0months, all p < 0.01) increased significantly, except for patients who had <6 LNs harvested. On multivariable survival analysis, a higher nodal stage (N1 vs. N0: CSS, hazard ratio [HR] 2.135, 95% CI 1.636-2.788, p < 0.001; OS, HR 2.100, 95% CI 1.624-2.717, p < 0.001; N2 vs. N0: CSS, HR 4.027, 95% CI 2.791-5.811, p < 0.001; OS, HR 3.678, 95% CI 2.561-5.282, p < 0.001) was an independent prognostic risk factor for survival. Despite the lack of a clear survival benefit of LND in patients with ICC, a significant positive association between the number of LNM and poor outcomes was observed. We still suggest adequate LND by examining at least six LNs to ensure precise staging. On this basis, the recently proposed nodal classification of N0, N1, and N2 stages may also allow better prognostic stratification of ICC patients.

Prognostic outcomes of cytomegalovirus reactivation after autologous stem cell transplantation.

Background: Cytomegalovirus (CMV) reactivation is a common complication in patients undergoing allogeneic stem cell transplantation. However, the incidence of CMV reactivation is low after autologous stem cell transplantation (auto-SCT), and the prognostic value of CMV reactivation remains controversial. Moreover, reports on late CMV reactivation after auto-SCT are limited. We aimed to analyze the association between CMV reactivation and survival outcomes and develop a predictive model for late CMV reactivation in patients undergoing auto-SCT. Methods: Data of 201 patients who underwent SCT at the Korea University Medical Center from 2007 to 2018 were collected. We analyzed prognostic factors for survival outcomes after auto-SCT and risk factors for late CMV reactivation using a receiver operating characteristic curve. Then, we developed a predictive risk model for late CMV reactivation based on results of the risk factor analysis. Results: Early CMV reactivation was significantly associated with better overall survival (OS) (hazard ratio [HR], 0.329; P = 0.045) in patients with multiple myeloma; however, no significant differences were observed in patients with lymphoma. For late CMV reactivation, a serum lactate dehydrogenase level greater than the upper limit of normal (HR, 2.251; P = 0.027) and late CMV reactivation (HR, 2.964; P = 0.047) were independent risk factors for poor OS, while lymphoma diagnosis (vs. multiple myeloma; HR, 0.389; P = 0.016) was an independent risk factor for good OS. In risk factor analysis for late CMV reactivation, T-cell lymphoma diagnosis (odds ratio [OR], 8.499; P = 0.029), ≥ two prior chemotherapies (OR, 8.995; P = 0.027), failure to achieve complete response (CR) after transplantation (OR, 7.124; P = 0.031), and early CMV reactivation (OR, 12.853; P = 0.007) were significantly associated with late CMV reactivation. To develop the predictive risk model for late CMV reactivation, a score (1 to 1.5) was assigned for each of the above-mentioned variables. The optimal cutoff value (1.75 points) was calculated using the receiver operating characteristic curve. The predictive risk model showed good discrimination, with an area under the curve of 0.872 (standard error, 0.062; P < 0.001). Conclusions: Late CMV reactivation was an independent risk factor for inferior OS, whereas early CMV reactivation was associated with better survival in patients with multiple myeloma. This risk prediction model could be helpful in identifying high-risk patients who require monitoring for late CMV reactivation and potentially benefit from prophylactic or preemptive therapy.