Relapse-free Survival Outcomes Research Articles

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258.

Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT). GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype. ECs classified as deficient MMR (dMMR) (27%), p53 abnormal (p53abn) (24%), and p53 wild type (p53wt) (49%). p53abn were more frequent in patients that were older, Black, and had serous histology (p<0.001). Median follow up was 113months. Five-year RFS and OS were worse with p53abn (29% [Hazard Ratio (HR)=3.39 (95% Confidence Interval (CI): 2.34-4.91)] and 39% [HR=4.64 (95% CI: 3.16-6.79)] compared to those with p53wt (referent) (p<0.001). The five-year RFS and OS for dMMR cancers were (58% [HR=1.30 (95% CI: 0.85-1.97)] and 77% [HR=1.53 (95% CI: 0.99-2.36)] compared to those with p53wt (69% and 85%). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77% vs 60%; HR=0.54 (95% CI: 0.32-0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups. Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.

Pretransplant Chromosome Genomic Array Testing Improves Prognosis for Myelofibrosis Patients Undergoing Transplantation.

Despite its known superior diagnostic yield for chromosomal anomalies compared with karyotype and fluorescence in situ hybridization (FISH) studies, chromosome genomic array testing (CGAT) is not used as a routine clinical test for myelofibrosis. Although many prognostic systems exist that risk stratify patients at diagnosis, limited tools are available to prognosticate transplant outcome. The current study aimed at testing whether CGAT results obtained before transplantation improves prognosis of post-transplant outcome in patients with myelofibrosis compared with current risk categorization systems, for example, DIPSS plus (Dynamic International Prognostic Scoring System). We studied patients with myelofibrosis who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (N = 44). We assessed the prognostic significance of CGAT, DIPSS plus, and the total count of gene mutations for post-transplant clinical outcomes, including relapse-free survival (RFS), overall survival (OS), and graft-versus-host-disease (GVHD). Abnormal CGAT results were seen in 24 patients (55%), including 18 with copy-neutral loss of heterozygosity (cnLOH, 41%). With a median follow-up of 91 (range 2-258) months starting from the CGAT sample date, RFS was 59% and OS was 68%. The outcome analysis showed significant prognostic implication from CGAT (normal vs. abnormal), specifically for patients with intermediate risk by DIPSS-plus scores and those with 0∼2 mutations. CGAT alone significantly stratified the patients' RFS outcome (P = .03). The addition of CGAT to DIPSS-plus improved the significance from a P value of .08 to .003, whereas the addition of CGAT to mutation count improved the P value from .02 to .01. The best stratification system for RFS was achieved when CGAT, DIPSS-plus, and mutation count were all considered (P = 1e-08). The current study also confirmed individual anomalies that are prognostically significant, including U2AF1 mutation (n = 5, P = .03) and 1q gain (n = 3, P = .01), which were associated with worse RFS. ASXL1 mutations (n = 14) appeared to associate with a later onset of chronic GVHD (P =.03). Pretransplant CGAT analysis augments the existing risk stratification tools and may be considered as routine clinical testing for myelofibrosis.

Differential predictive value of tissue-specific PD-L1 expression scores in adjuvant immunotherapy of melanoma.

Adjuvant treatment of stage II-IV melanoma with PD-1-based immune checkpoint inhibitors (ICI) has improved relapse-free survival (RFS) and has therefore become a standard-of-care treatment option. Approximately 25%-30% of patients still recur within 1 year. Predictive biomarkers reflecting real-world data are desired. The predictive relevance of tumour tissue PD-L1 expression in the adjuvant setting remains inconclusive. This retrospective, observational study was conducted to evaluate the value of PD-L1 expression scores in different tumour tissue locations in predicting response towards adjuvant immunotherapeutic treatment. Tumour tissue taken prior to anti-PD-1 adjuvant ICI in 243 stage II-IV melanoma patients was collected at University Skin Cancer Center Hamburg. PD-L1 expression was evaluated on immune cells (ICS), tumour cells (TPS) and combined (CPS). Scores were determined by independent pathological physician quantification and correlated with therapy outcome at different cut-off (CO) levels (relapse-free survival, RFS) for different tumour tissue locations (primary tumour, metastases). A total of 104 patients were eligible for analysis. Positivity of ICS, TPS and CPS showed no predictive RFS outcome association at different CO levels when analysed irrespective of tissue origin. In primary tumours, ICS at CO 1% showed a significantly improved RFS upon positivity (HR 0.22). In contrast, positivity to TPS (CO 1%) correlated significantly and independently with improved RFS when evaluated in metastatic tumour tissue specimens (HR 0.37). PD-L1 tumour tissue expression may serve as a predictive biomarker for adjuvant ICI treatment response stratification in melanoma, but caution should be spent on the origin of tumour tissue analysed. The cell-type relevant for the predictive value of PD-L1 expression is tissue-specific with immune cells being important in primary tumours while tumour cells are key in metastases. The present results should be validated in a multicentre cohort.

Significance of Pre-Treatment CALLY Score Combined with EBV-DNA Levels for Prognostication in Non-Metastatic Nasopharyngeal Cancer Patients: A Clinical Perspective.

The C-reactive protein-albumin-lymphocyte (CALLY) score is a novel indicator associated with inflammation, immunity, and nutrition, utilized for cancer prognostic stratification. This study aimed to evaluate the integrated prognostic significance of the pre-treatment CALLY score and Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) patients and to develop prognostic models. A total of 1707 NPC patients from September 2015 to December 2017 were retrospectively enrolled. The cut-off point for the CALLY score, determined by maximum selected rank statistics, integrates with the published cut-off point for pre-EBV DNA to develop a comprehensive index. Subsequently, patients were randomly allocated in a 1:1 ratio into training and validation cohorts. Survival analysis was conducted using the Kaplan-Meier method with Log rank tests, and the Cox proportional hazards model was applied to identify independent prognostic factors for constructing predictive nomograms. The predictive ability of the nomograms were assessed through the concordance index (C-index), calibration curves, and decision curve analysis. By integrating CALLY scores and EBV-DNA levels, patients were categorized into three risk clusters. Kaplan-Meier curves reveal significant differences in overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) outcomes among different risk groups (all P values < 0.05). Multivariate analysis revealed that CALLY-EBV DNA index serves as an independent prognostic factor for the OS, DMFS, and LRRFS. The prognostic nomograms based on the CALLY-EBV DNA index provided accurate predictions for 1-year, 3-year, and 5-year OS, DMFS, and LRRFS. Additionally, compared to the traditional TNM staging system, the nomograms exhibited enhanced discriminatory power, calibration capability, and clinical applicability. All results were in agreement with the validation cohort. The CALLY-EBV DNA index is an independent prognostic biomarker. The nomogram prediction models, constructed based on the CALLY-EBV DNA index, demonstrates superior predictive performance compared to the traditional TNM staging.

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes-BAALC, HHEX, MEF2C, FAT1, LYL1, LMO2, LYN, and TAL1; (ii) epigenetic modifiers-DOT1L, EP300, EML4, RAG1, EZH2, and KDM6A; and (iii) long noncoding RNAs (lncRNAs)-XIST, PCAT18, PCAT14, LINC00202, LINC00461, LINC00648, ST20, MEF2C-AS1, and MALAT1 in an independent cohort of 99 patients with T-ALL. Principal component analysis revealed distinct clusters aligning with immunophenotypic subtypes, providing insights into the molecular heterogeneity of T-ALL. The identified signature genes exhibited associations with clinicopathologic features. Survival analysis uncovered several independent predictors of patient outcomes. Higher expression of MEF2C, BAALC, HHEX, and LYL1 genes emerged as robust indicators of poor overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). Higher LMO2 expression was correlated with adverse EFS and RFS outcomes. Intriguingly, increased expression of lncRNA ST20 coupled with RAG1 demonstrated a favorable prognostic impact on OS, EFS, and RFS. Conclusively, several hitherto unreported associations of gene expression patterns with clinicopathologic features and prognosis were identified, which may help understand T-ALL's molecular pathogenesis and provide prognostic markers.

Abemaciclib combined with endocrine therapy as adjuvant treatment for hormone-receptor-positive, HER2-, high-risk early breast cancer: 5-year Chinese population analysis of the phase III randomized monarchE study.

Abemaciclib was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved globally in the adjuvant setting for high-risk hormone-receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) early breast cancer (EBC), based on the phase III monarchE trial. To report an exploratory Chinese population analysis based on the preplanned overall survival (OS) interim analysis with 5-year efficacy results of monarchE. Patients with HR+/HER2-, high-risk (⩾4 positive lymph nodes, or 1-3 nodes and either tumor size ⩾5 cm, histologic grade 3, or Ki-67 ⩾20%) EBC were randomized (1:1) to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy (ET), or ET alone. This analysis included Chinese patients enrolled in mainland China, Hong Kong, and Taiwan. The primary endpoint was invasive disease-free survival (IDFS); key secondary endpoints included distant relapse-free survival (DRFS), safety, and patient-reported outcomes (PROs). Overall, 501 Chinese patients were included (abemaciclib + ET, n = 259; ET, n = 242). With a median follow-up of 53 months, the addition of abemaciclib to ET resulted in improvements in IDFS (estimated 5-year IDFS rate: 85.9% vs 79.1%; hazard ratio (HR), 0.65 (95% confidence interval (CI) 0.41-1.03)) and DRFS (estimated 5-year DRFS rate: 88.4% vs 82.3%; HR, 0.65 (95% CI, 0.39-1.07)). The most common grade ⩾3 treatment-emergent adverse events in the abemaciclib + ET versus ET groups were neutropenia (24.7% vs 0.8%) and leukopenia (22.4% vs 0.4%). Generally, no clinically meaningful difference in PROs (endocrine symptoms and fatigue) was observed between groups, except for diarrhea. At this prespecified OS interim analysis, which provides 5-year data, the addition of abemaciclib to ET in Chinese patients with high-risk HR+, HER2- EBC was associated with sustained and clinically meaningful improvements in IDFS and DRFS, with acceptable safety and tolerability profiles and minimal impact on PROs. These results represent the first full report of a CDK4/6 inhibitor in Chinese patients with EBC and support the positive benefit-risk profile of adjuvant abemaciclib + ET in Chinese patients. ClinicalTrials.gov identifier: NCT03155997 (first posted: May 16, 2017).

The salvage role of allogeneic hematopoietic stem-cell transplantation in relapsed/refractory diffuse large B cell lymphoma

To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.

SPAG5 Expression Predicts Poor Prognosis and is Associated With Adverse Immune Infiltration in Lung Adenocarcinomas.

Sperm-associated antigen 5 (SPAG5) has been identified as a novel driver oncogene involved in multiple cancers; however, its role in lung adenocarcinoma (LUAD) needs further investigation. Our study aims to elucidate the potential significance of SPAG5 in LUAD prognosis and its implications for the efficacy of immunotherapy. In this study, we used bioinformatics analysis and tissue microarray (TMA) staining to examine the potential role of SPAG5 in LUAD survival and response to immunotherapy. We used the Oncomine, TIMER2.0, Gene Expression Profiling Interactive Analysis (GEPIA), Sangerbox, PredicScan, and Kaplan-Meier Plotter databases to examine the expression and prognostic role of SPAG5 in the LUAD of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other databases. We also used Cancer Single-cell State Atlas (CancerSEA) and Tumor Immune Estimation Resource (TIMER2.0) to analyze the association of SPAG5 with malignant phenotype and tumor immune microenvironment. Furthermore, Immune Cell Abundance Identifier (ImmuCellAI) analysis of TCGA sequencing data was used to predict the role of SPAG5 in determining the response to immune checkpoint blockade (ICB) treatment in LUAD. Co-expression analysis of programmed death-ligand 1 (PD-L1) and SPAG5 was performed using LUAD TMA immunohistochemistry (IHC) analysis. Our findings indicate that SPAG5 is overexpressed in LUAD and is positively correlated with advanced clinical stage, poor overall survival, relapse-free survival, and progression-free survival outcomes. SPAG5 may be involved in regulating the cell cycle, proliferation, invasion, DNA damage and repair, and tumor immunosuppression. Furthermore, TMA IHC analysis showed a positive correlation between PD-L1 expression in LUAD and SPAG5 which suggests that SPAG5 may serve as a potential predictor of response to ICB therapy in LUAD. Our results highlight the role of SAPG5 in promoting a tumor malignancy phenotype and immunosuppression in LUAD and suggest that SPAG5 may serve as a potential response marker for ICB therapy.

Improved Gvhd and Relapse Free Survival Outcomes in Older Acute Leukemia Patients Receiving Young Haploidentical Donor Vs Older Matched Sibling Donor Reduced Intensity Conditioning Hematopoietic Cell Transplants

Background: Allogeneic hematopoietic cell transplants (alloHCT) from HLA-matched sibling donors (MSD) or matched unrelated donors (MUD) may cure patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndromes (MDS). Older patients with AML benefit from alloHCT, but donor selection may be complicated by the advanced age and comorbidities of HLA-matched siblings. Haploidentical (Haplo) HCT with post-transplant cyclophosphamide (PTCy) is an alternative approach to traditional HLA-matched alloHCT. HaploHCT is associated with reduced graft-versus-host disease (GVHD) risk but reduced overall survival (OS) in some series with older recipients. There are limited published data assessing outcomes using younger Haplo donors versus older MSD for older HCT recipients. The objective of this study is to characterize treatment outcomes and GVHD rates in older HCT recipients of younger HaploHCT compared to older MSD grafts. Methods: This retrospective cohort analysis included patients aged 50 years and older with AML, ALL, or MDS who received reduced intensity conditioning (RIC) and either a young Haplo donor or older MSD graft from 2014 to 2020. Young donors included those <50 years old, and older donors were ≥50 years old. The primary outcome was OS one-year post-HCT. Secondary analyses included aGVHD and cGVHD outcomes, relapse-free survival (RFS), GVHD-RFS (GRFS), non-relapse mortality (NRM), infection incidence, time to neutrophil recovery, and relapse incidence. Kaplan-Meier method with log-rank test was used to assess OS, RFS, and GRFS. All data presented are organized as Haplo versus MSD. Results: Twenty-nine patients received younger donor Haplo grafts and 47 patients received older MSD grafts. Median age for donors was 35.4 years vs 61.6 years in the Haplo and MSD cohort, respectively. The underlying hematologic disorder leading to alloHCT in the two cohorts were AML (83% vs 47%), ALL (3% vs 11%), and MDS (28% vs 43%) (p<0.001). Stratified cytogenetic risk categories for each diagnosis were not significantly different. RIC regimens included Fludarabine (Flu)/Melphalan or Flu/Busulfan for older MSD recipients, whereas the younger donor Haplo cohort received Flu/Cy/TBI (200cGy). PTCy/Tacrolimus (Tac) was the GVHD prophylaxis (ppx) regimen for all Haplo recipients, whereas 96% of MSD cohort got Tac/Methotrexate (MTX) and 4% of MSD cohort got Tac/MTX/MMF. Peripheral blood was the graft source in 62% of HaploHCT and 100% of MSD (p<0.001). Seventy-six percent of donors in the Haplo cohort were recipient offspring. One-year OS was 86% vs 72% (p=0.27), RFS was 69% vs 70% (p=0.76), NRM was 7% vs 9% (p=0.86), and GRFS 89% vs 62% (p=0.005) [Table 1] for Haplo vs MSD cohorts, respectively. Median OS (HR 0.88, p=0.785) and median RFS (HR 1.38, p=0.459) were not reached in either group. Median GRFS was longer in the Haplo cohort (190 vs 148 days, HR 0.52, p=0.021) [Figure 1]. One-year incidence of relapse was not different between cohorts (p=0.14). Incidence of aGVHD (38% vs 32%, p=0.51) was similar in both cohorts, although maximum aGVHD grade was lower in the Haplo group (p=0.04). cGVHD incidence numerically favored HaploHCT (45% vs 66%, p=0.08) [Table 1]. Individuals receiving HaploHCT had a longer median time to neutrophil engraftment (19 vs 14 days, p<0.001) and a shorter median time to full CD3 chimerism (32 vs 76.5 days, p<0.001). They also had a higher incidence of CMV viremia (p=0.014), BK viremia (p=0.05), and fungal infections (p=0.047) [Table 1]. Incidence of HHV6 (p=0.18) and EBV viremia (p=0.89) were not different between cohorts. Discussion: Our results demonstrate similar OS, RFS and incidence of aGVHD and cGVHD between younger donor HaploHCT and older MSD alloHCT for older patients. GRFS was significantly better in the Haplo cohort, which may have been primarily influenced by higher incidence of cGVHD and higher grades of aGVHD observed for recipients of older MSD grafts with Tac/MTX-based GVHD ppx. aGVHD and cGVHD rates may be reduced with the use of HaploHCT and incorporation of PTCy at the expense of more opportunistic infections. Our results suggest that young donor HaploHCT using PTCy may be a reasonable alternative for alloHCT and reduce risks for GVHD for older patients with leukemia even if a MSD is available. These data also suggest MSD alloHCT with PTCy should be explored. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Bioinformatics Analysis of the Prognostic Significance of CAND1 in ERα-Positive Breast Cancer.

The identification of novel prognostic biomarkers for breast cancer is an unmet clinical need. Cullin-associated and neddylation-dissociated 1 (CAND1) has been implicated in mediating carcinogenesis in prostate and lung cancers. In addition, CAND1 is an established prognostic biomarker for worse prognosis in liver cancer. However, the prognostic significance of CAND1 in breast cancer has not yet been explored. In this study, Breast Cancer Gene-Expression Miner (Bc-GenExMiner) and TIMER2.0 were utilized to explore the mRNA expression of CAND1 in ERα-positive breast cancer patients. The Kaplan–Meier plotter was used to explore the relationship between CAND1 expression and several prognostic indicators. The Gene Set Cancer Analysis (GSCA) web server was then used to explore the pathways of the genes that correlate with CAND1 in ERα-positive breast cancer. Immune infiltration was investigated using Bc-GenExMiner. Our bioinformatics analysis illustrates that breast cancer patients have higher CAND1 compared to normal breast tissue and that ERα-positive breast cancer patients with a high expression of CAND1 have poor overall survival (OS), distant metastasis-free survival (DMFS), and relapse-free survival (RFS) outcomes. Higher CAND1 expression was observed in histologic grade 3 compared to grades 2 and 1. Our results revealed that CAND1 positively correlates with lymph nodes and negatively correlates with the infiltration of immune cells, which is in agreement with published reports. Our findings suggest that CAND1 might mediate invasion and metastasis in ERα-positive breast cancer, possibly through the activation of estrogen and androgen signaling pathways; however, experiments should be carried out to further explore the role of CAND1 in activating the androgen and estrogen signaling pathways. In conclusion, the results suggest that CAND1 could be used as a potential novel biomarker for worse prognosis in ERα-positive breast cancer.

806P Updated toxicity profile and relapse-free survival outcomes using an adapted pyrexia management algorithm in patients with resected stage III BRAF V600E/K-mutant melanoma treated with adjuvant dabrafenib plus trametinib in COMBI-APlus

COMBI-APlus (NCT03551626) evaluated an adapted pyrexia management algorithm in patients (pts) with resected stage III BRAF V600E/K-mutant melanoma treated with adjuvant dabrafenib plus trametinib (D + T). The study showed significant improvement in the composite pyrexia events compared to that in COMBI-AD. Here we report the updated long-term toxicity profile and relapse-free survival (RFS) from COMBI-APlus.

Association of serum reproductive hormones changes after neoadjuvant chemotherapy with hormone receptors expression alterations and survival outcomes in breast cancer.

PurposeThis study aimed to determine the effect of neoadjuvant chemotherapy (NAC) on circulating levels of reproductive hormones and evaluate the correlation of hormone changes after NAC with hormone receptors expression alterations and relapse-free survival (RFS) outcomes in breast cancer.MethodsInformation from 181 breast cancer patients who received NAC was retrospectively analyzed. For hormones parameters, the median and interquartile range (IQR) were provided at baseline and the end of NAC then was compared by Wilcoxon signed-rank test. Categorical variables were represented as numbers and percentages and were compared via two-sided chi-square and Fisher's tests. The RFS outcomes were compared between patients according to hormone changes using the log-rank test. Univariate and multivariate survival analyses with hazard ratios (HR) and 95% confidence intervals (95% CI) were carried out using Cox regression.ResultsSex steroids including estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate (DHEAS) levels decreased significantly after NAC among both premenopausal and postmenopausal patients (all P < 0.05). Decreased estradiol levels were associated with reduced progesterone receptor (PR) expression (P = 0.030). In multivariate survival analysis, the non-decreased progesterone level was strongly associated with worse RFS (non-decreased vs. decreased, HR = 7.178, 95% CI 2.340–22.019, P = 0.001). Patients with decreased progesterone levels exhibited better 3-year RFS compared with those with non-decreased (87.6% vs. 58.3%, log-rank, P = 0.001).ConclusionMultiple reproductive hormone levels were influenced by NAC. The change in estradiol level had a positive connection with PR expression alteration. Furthermore, an inverse association between the change in progesterone level and RFS outcomes was found. These findings may provide a theoretical basis for pre-operative endocrine therapy combined with NAC in breast cancer patients.

Analysis of overall survival (OS) and relapse-free-survival (RFS) in the phase 1b clinical trial of anti–PD-1 ab (toripalimab) plus intralesional injection of OrienX010 in stage Ⅳ melanoma with liver metastases.

9551 Background: Advanced melanoma with liver metastasis has reduced response to anti-PD-1 monotherapy with ORR of 4.3% in a pooled analysis, and initial results of the phase 1b trial, systemic toripalimab combined with intrahepatic OrienX010 injection - a HSV-1-derived oncolytic virotherapy with expression of GM-CSF had shown its efficacy. Here we report the RFS and OS outcomes. Methods: Eligible pts included those over 18 with injectable liver metastasis confirmed by biopsy with or without extra-hepatic metastasis; the ocular melanoma and brain metastasis were excluded. Pts received intravenous toripalimab Q2W combined with ultrasound guided intratumoral injection of OrienX010 Q2W (8×107 pfu/ml, 10ml per injection) until intolerance or disease progression per iRECIST criteria. Liver biopsy would be performed at baseline and first tumor evaluation (8-12weeks). The primary endpoint was toxicity; secondary endpoints included ORR, DCR and PFS. Results: From Jul 2019 to Jan 2022, 23 pts were eligible and enrolled. Baseline characteristics: median age 69 yrs; primary: mucosal 60.9%, cutaneous 13.0%, unknown primary 13.0%, acral 13.0%; gene mutation status: Braf 17.4%, Nras 4.3%; 69.6% got extra-hepatic metastasis: regional or distant lymph node 56.3%, lung 37.5%, bone 31.3%; LDH＞ULN 26.1%; median size of injected lesions: 35mm(10-94mm); median number of liver metastasis: 7(1-10); median number of injection: 10 (3-36). Among these pts, 20 pts could be evaluated for efficacy. The median PFS was 7.0 months (95%CI: 4.3-9.7 months) and the median OS was 18.6 months (95%CI: 13.4-23.7 months) with a median follow-up time of 19.8 months (range, 0.9-29.7). The global ORR by investigator was 15% (3/20), DCR 50% (10/20); the response rate was 35%(7/20) for injected lesions, 27.8%(5/18) for non-injected lesions in liver, and 26.7% (4/15) for extra-hepatic metastases. Biopsies of 15 pts for injected lesions at 8 to 12 weeks after first injection were examined to determine the situation of TIL infiltration. Among them, the median PFS of the pts (7/15) with impressive TIL infiltration (Brisk n = 4 and Nonbrisk n = 3 according to the definition of AJCC 8th edition) was 7.8 months (95%CI: 2.8-12.8 months) versus 4.1 months (95%CI: 0-9.1 months) of the pts without impressive TIL infiltration. For pts（21.7%( 2 PR and 3 SD)）with no melanoma cells residual by immunohistochemistry in biopsies the median PFS was 13.8 months (95%CI: 4.0-23.6 months), and it was much longer than that of other pts which was 5.6 months (95%CI: 2.4-8.8 months). The median OS of the pts with no melanoma cells was 19.7 months (95%CI: 7.5-31.9 months). Conclusions: Systemic toripalimab combined with intrahepatic OrienX010 injection has shown remarkable long PFS and OS in melanoma pts with liver metastases. Clinical trial information: NCT04206358.

Treatment of bulky lymph nodes in locally advanced cervical cancer: boosting versus debulking

ObjectiveTreatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this...

Prognostic implications of tumor-infiltrating T cells in early-stage endometrial cancer

Patients with endometrial cancer differ in terms of the extent of T-cell infiltration; however, the association between T-cell subpopulations and patient outcomes remains unexplored. We characterized 285 early-stage endometrial carcinoma samples for T-cell infiltrates in a tissue microarray format using multiplex fluorescent immunohistochemistry. The proportion of T cells and their subpopulations were associated with clinicopathological features and relapse-free survival outcomes. CD3+ CD4+ infiltrates were more abundant in the patients with higher grade or non-endometrioid histology. Cytotoxic T cells (CD25+, PD-1+, and PD-L1+) were strongly associated with longer relapse-free survival. Moreover, CD3+ PD-1+ stromal cells were independent of other immune T-cell populations and clinicopathological factors in predicting relapses. Patients with high stromal T-cell fraction of CD3+ PD-1+ cells were associated with a 5-year relapse-free survival rate of 93.7% compared to 79.0% in patients with low CD3+ PD-1+ fraction. Moreover, in patients classically linked to a favorable outcome (such as endometrioid subtype and low-grade tumors), the stromal CD3+ PD-1+ T-cell fraction remained prognostically significant. This study supports that T-cell infiltrates play a significant prognostic role in early-stage endometrial carcinoma. Specifically, CD3+ PD-1+ stromal cells emerge as a promising novel prognostic biomarker.

Long-term outcomes of standardized colonic stenting using WallFlex as a bridge to surgery: Multicenter prospective cohort study.

ObjectivesThe oncological outcomes, especially high recurrence rate, of bridge‐to‐surgery (BTS) self‐expandable metallic stent (SEMS) placement remain concerning, emphasizing the necessity of standardized SEMS placement. However, its impact on long‐term BTS outcomes is unknown. We investigated the long‐term outcomes of BTS colonic stenting using standardized SEMS placement.MethodsThis prospective, multicenter cohort study conducted at 46 hospitals in Japan (March 2012 to October 2013) included consecutive patients with stage II and III obstructive colorectal cancer managed with BTS SEMS placement. The SEMS placement technique was standardized by information dissemination among the participating hospitals. The primary outcome was overall survival (OS) after SEMS placement, and the secondary outcomes were relapse‐free survival (RFS), recurrence, and short‐term outcomes of SEMS placement and surgery.ResultsThe 1‐, 3‐, and 5‐year OS rates were 94.1%, 77.4%, and 67.4% (Kaplan–Meier), respectively, with high technical success (99.0%, 206/208) and low perforation (1.9%, 4/208) rates. The 1‐, 3‐, and 5‐year RFS rates were 81.6%, 65.6%, and 57.9% (Kaplan–Meier), respectively, and the overall recurrence rate was 31.0% (62/200). The RFS rate was significantly poorer in patients with perforation (n = 4) than in those without perforation (n = 196) (log‐rank P = 0.017); moreover, perforation was identified as an independent factor affecting RFS (hazard ratio 3.31; 95% confidence interval 1.03–10.71, multivariate Cox regression).ConclusionThis large, prospective, multicenter study revealed satisfactory long‐term outcomes of BTS colonic stenting using a standardized SEMS insertion method, which might be specifically due to the reduced perforation rate. (UMIN000007953).

Evaluation of patients with surgically resected high-risk melanoma receiving adjuvant therapy in routine clinical practice in the United States.

9577 Background: The management of patients with resected stage III melanoma has changed in recent years, and real-world data on recurrence patterns and adjuvant therapy responses are scarce. This study assessed adjuvant treatment patterns and outcomes in patients with advanced melanoma by BRAF status and relapse location. Methods: Patients diagnosed with stage III advanced melanoma between January 2011 and February 2020 in the nationwide Flatiron Health electronic health record–derived deidentified database were included if they were ≥18 years, received approved first-line (1L) adjuvant therapy after January 2018 with checkpoint inhibitors (CPIs; eg, nivolumab, pembrolizumab) or targeted therapies (TTs; eg, dabrafenib/trametinib), had 6 months’ follow-up and had ≥1 visit after starting adjuvant therapy (Cohort 1). Patients from Cohort 1 were included in Cohort 2 if they had a recurrence following initiation of adjuvant therapy, and those from Cohort 2 were included in Cohort 3 if they had a distant recurrence and available documented BRAF status at any time. Time to next systemic treatment (TTNT), overall survival (OS) and relapse free survival (RFS) were estimated using Kaplan-Meier (KM) methods from adjuvant therapy start (Cohort 1), first recurrence date (Cohort 2) or first distant recurrence date (Cohort 3). Results: Cohort 1 included 447 patients receiving 1L adjuvant therapy; Cohort 2 included patients after first distant (n = 47) or local (n = 35) relapse; Cohort 3 included distant-recurrent patients with tumors that were BRAF wild type (WT) (n = 22) or BRAF mutant (n = 23). The majority of patients were aged &lt; 65 years. Across cohorts, relative use of TTs vs CPIs was similar: Cohort 1 (4.5% vs 96%), Cohort 2 (2.4% vs 98%) and Cohort 3 (2.2% vs 98%). Nivolumab was the most frequent treatment used across cohorts (84%-88%). In Cohort 1, 1- and 2-year KM probabilities for OS, RFS and TTNT were 93.5%/83.8%, 83.2%/70.6% and 84.0%/62.4%, respectively. In Cohort 2, for patients with local recurrence, 6- and 12-month OS probabilities were 93.4% and 78.8%, respectively, which were substantially higher than those for patients with distant recurrence (64.5% and 46.9%). In Cohort 3, for patients with documented BRAF mutations, 6- and 12-month OS rates from disease recurrence were 79.1% and 49.4%, respectively, which were greater than for those with BRAF-WT tumors (54.1% and 46.3%). Conclusions: Early RFS and OS outcomes for patients with surgically resected Stage III melanoma appear comparable to those reported in randomized clinical studies. The majority of patients with advanced melanoma, including patients who experienced recurrence, initiated treatment with CPIs. OS rates were numerically greater for Cohort 3 patients with BRAF-mutant tumors. Outcomes for patients with distant recurrence after adjuvant therapy remain unfavorable and represent a continued unmet medical need.

Immune adverse events (irAEs) with adjuvant ipilimumab in melanoma, use of immunosuppressants and association with outcome: ECOG-ACRIN E1609 study analysis

BackgroundThe impact of immune-related adverse events (irAEs) occurring from adjuvant use of immunotherapy and of their management on relapse-free survival (RFS) and overall survival (OS) outcomes is currently not well...

Survival outcomes for breast cancer patients who decline recommended treatment: a propensity score-matched analysis.

For patients with breast cancer who decline recommended treatments, available data examining survival outcomes are sparse. We compared overall survival and relapse-free survival outcomes between patients with breast cancer who declined recommended primary treatments and those who received recommended primary treatments. Using data from the BreastSurgANZ Quality Audit database, a retrospective cohort study was performed for patients diagnosed with breast carcinoma (stage 0-IV) between 2001 and 2014 who were treated in our integrated cancer centre. A propensity score-matched analysis was performed to compare overall survival and relapse-free survival between patients who either declined or received the standard recommended treatment. A total of 56/912 (6.1%) patients declined one or more recommended therapies. Five-year overall survival for those who declined or received treatment as recommended was 81.8% versus 88.9% (P=0.17), respectively. Ten-year survival was 61.3% versus 67.8% (P=0.22), respectively. For patients who declined treatments, 5-year relapse-free survival was 72.4%, compared to 87.4% for those who received them (P=0.005). Ten-year relapse-free survival was 61.0% versus 80.6% (P=0.002), respectively. On adjusted Cox regression analysis, treatment refusal was associated with poorer relapse-free survival (adjusted hazard ratio 2.76 (95% confidence interval 1.52-5.00), P < 0.001). In conclusion, patients who declined recommended treatment for breast cancer had poorer relapse-free survival compared to those who received them. These data may help clinicians assist patients with breast cancer in their decision-making.

Integrated bioinformatic analysis identifies UBE2Q1 as a potential prognostic marker for high grade serous ovarian cancer

BackgroundHigh grade serous ovarian cancer (HGSOC) accounts for nearly 60% of total cases of epithelial ovarian cancer. It is the most aggressive subtype, which shows poor prognosis and low patient survival. For better management of HGSOC patients, new prognostic biomarkers are required to facilitate improved treatment strategies and ensure suitable healthcare decisions.MethodsWe performed genome wide expression analysis of HGSOC patient samples to identify differentially expressed genes (DEGs) using R based Limma package, Clust and other statistical tools. The identified DEGs were subjected to weighted gene co-expression network analysis (WGCNA) to identify co-expression patterns of relevant genes. Module trait and gene ontology analyses were performed to establish important gene co-expression networks and their biological functions. Overlapping the most relevant DEG cluster 4 with prominent WGCNA cyan module identified strongest correlation of UBE2Q1 with ovarian cancer and its prognostic significance on survival probability of ovarian cancer patients was investigated. The predictive value of UBE2Q1 as a potential biomarker was analysed by correlating its expression with 12-months relapse free survival of patients in response to platin/taxane, the standard first-line chemotherapy for ovarian cancer, and analysing area under the ROC curve.ResultsAn integrated gene expression analysis and WGCNA, identified UBE2Q1 as a potential prognostic marker associated with poor relapse-free survival and response outcome to platin/taxane treatment of patients with high grade serous ovarian cancer.ConclusionsOur study identifies a potential UBE2Q1 – B4GALT3 functional axis in ovarian cancer, where only the E2 conjugating enzyme showed a poor prognostic impact on the disease.