Independent Prognostic Factor For Disease-free Survival Research Articles

The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (> 2cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study.

The use of adjuvant osimertinib for epidermal growth factor receptor (EGFR) mutants is expected to expand to earlier stage I in the future, potentially competing with the current standard of care, oral tegafur/uracil (UFT), in Japan. However, the effect of EGFR mutation status on the therapeutic effect of UFT remains unclear. This study was conducted as an exploratory analysis of a retrospective observational study that investigated the real-world data of postoperative adjuvant chemotherapy in Japan (CSPOR-LC03). Between 2008 and 2013, 1812 patients with completely resected adenocarcinoma diagnosed as pathologic stage I (T1>2cm, TNM classification, sixth edition) who have maintained organ function, and no history of other cancers were included. The primary endpoint was the 5-year disease-free survival (DFS) rate, and we compared this rate between four groups classified based on the administration of adjuvant UFT and EGFR mutation status. Of the 933 (51%) patients with EGFR mutations, 394 underwent adjuvant UFT therapy. Of the 879 (49%) patients without EGFR mutations, 393 underwent adjuvant UFT therapy. The 5-year DFS of UFT+/EGFR+ and UFT-/EGFR+ patients were 82.0 and 87.1%, respectively, and those of UFT+/EGFR- and UFT-/EGFR- patients were 80.0 and 86.9%, respectively. DFS was significantly worse in the UFT+ group than in the UFT- group (P=0.015). Adjuvant UFT therapy was not an independent prognostic factor for DFS, regardless of the EGFR mutation status. In pathologic stage I (>2cm) lung adenocarcinomas with EGFR mutation, the survival benefit of adjuvant UFT was not observed.

Oncological outcomes of minimally invasive surgery in non-endometrioid endometrial Cancer patients with varying prognostic risks: a retrospective cohort study based on the ESGO/ESTRO/ESP 2020 guidelines

BackgroundNon-endometrioid endometrial carcinomas (NEEC) are characterized by their rarity and adverse prognoses. This study evaluates the outcomes of open versus minimally invasive surgery (MIS) in NEEC patients stratified by prognostic risks according to the 2020 ESGO-ESTRO-ESP risk classification guidelines.MethodsA retrospective analysis was performed on 99 NEEC patients who underwent initial surgery at Fujian University Cancer Hospital. Patients were categorized into two groups: those undergoing MIS and those undergoing open surgery. We compared disease-free survival (DFS) and overall survival (OS) between these groups. Cox regression analysis was employed to identify risk factors for DFS, which were further validated via bootstrap statistical methods.ResultsThe study included 31 patients in the MIS group and 68 in the open surgery group. The demographics and clinical characteristics such as age, body mass index, comorbidities, histological subtypes, and FIGO stage were similar between groups (P > 0.05). The MIS group experienced ten recurrences (1 vaginal, 2 lymph nodes, 7 distant metastases), whereas the open surgery group had seven recurrences (1 vaginal, 3 lymph nodes, 1 pelvis, 2 distant metastases), yielding recurrence rates of 10.3% versus 25.6% (P = 0.007). Besides lymphovascular space invasion (LVSI), surgical approach was also identified as an independent prognostic factor for DFS in high-risk patients (P = 0.037, 95% CI: 1.062–7.409). The constructed nomogram demonstrated a robust predictive capability with an area under the curve (AUC) of 0.767. Survival analysis for high- and intermediate-risk patients showed no significant differences in OS between the two groups (Phigh risk = 0.275; Pintermediate−risk = 0.201). However, high-risk patients in the MIS group exhibited significantly worse DFS (P = 0.001).ConclusionThis investigation is the inaugural study to assess the impact of surgical approaches on NEEC patients within the framework of the latest ESGO-ESTRO-ESP risk classifications. Although MIS may offer clinical advantages, it should be approached with caution in high-risk NEEC patients due to associated poorer DFS outcomes.

236. THE ROLE OF ADJUVANT THERAPY FOLLOWING NEOADJUVANT CHEMORADIOTHERAPY AND ESOPHAGECTOMY IN ESOPHAGEAL CANCER

Abstract Background The objective of this study was to assess the role of adjuvant therapy following neoadjuvant chemoradiotherapy and esophagectomy in esophageal squamous cell carcinoma (ESCC). Methods We conducted a retrospective analysis involving 506 ESCC patients who underwent trimodal therapy. The clinical significance of adjuvant therapy on overall survival and disease-free survival was evaluated using Kaplan–Meier curves with log-rank tests, the Cox regression model, and a forest plot displaying hazard ratios (HR) with 95% confidence intervals. Results Among the 506 patients who had clinically positive lymph nodes and no metastasis after neoadjuvant chemoradiotherapy and esophagectomy, those who received adjuvant therapy exhibited shorter post-resection overall survival (OS) and disease-free survival (DFS), with a statistically significant difference between the two groups (Log-Rank, OS: P = 0.002; DFS: P < 0.001). Adjuvant therapy was not identified as an independent prognostic factor for OS (HR: 1.249; 95% CI: 0.869-1.796; P = 0.230), but it was a significantly unfavorable independent prognostic factor for DFS (HR: 1.868; 95% CI: 0.349-2.586; P < 0.001). Conclusion Adjuvant therapy is associated with poorer overall survival (OS) and disease-free survival (DFS) outcomes in ESCC patients with ypTNM stage I and II on final pathology following neoadjuvant chemoradiotherapy and esophagectomy. However, there was no significant difference observed in patients with ypTNM stage III or IV. Therefore, it is not recommended to undergo postoperative adjuvant therapy for patients with ypTNM stage I and II ESCC. However, for patients with ypTNM stage III and IV ESCC, further research is needed to explore adjuvant treatment strategies.

Comprehensive assessment of postoperative recurrence and survival in patients with cervical cancer

BackgroundThe prediction of postoperative recurrence and survival in cervical cancer patients has been a major clinical challenge. The combination of clinical parameters, inflammatory markers, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and MRI-derived radiomics is expected to support the prediction of recurrence-free survival (RFS), disease-free survival (DFS), tumor-specific survival (CSS), and overall survival (OS) of cervical cancer patients after surgery. MethodsA retrospective analysis of 181 cervical cancer patients with continuous follow-up was completed. The parameters of IVIM-DWI and radiomics were measured, analyzed, and screened. The LASSO regularization was used to calculate the radiomics score (Rad-score). Multivariate Cox regression analysis was used to construct nomogram models for predicting postoperative RFS, DFS, CSS, and OS in cervical cancer patients, with internal and external validation. ResultsClinical stage, parametrial infiltration, internal irradiation, D-value, and Rad-score were independent prognostic factors for RFS; Squamous cell carcinoma antigen, internal irradiation, D-value, f-value and Rad-score were independent prognostic factors for DFS; Maximum tumor diameter, lymph node metastasis, platelets, D-value and Rad-score were independent prognostic factors for CSS; Lymph node metastasis, systemic inflammation response index, D-value and Rad-score were independent prognostic factors for OS. The AUCs of each model predicting RFS, DFS, CSS, and OS at 1, 3, and 5 years were 0.985, 0.929, 0.910 and 0.833, 0.818, 0.816 and 0.832, 0.863, 0.891 and 0.804, 0.812, 0.870, respectively. ConclusionsNomograms based on clinical and imaging parameters showed high clinical value in predicting postoperative RFS, DFS, CSS, and OS of cervical cancer patients and can be used as prognostic markers.

Prognostic Value of Cancer-Associated Fibroblast Marker Expression in the Intratumoral and Marginal Areas of Soft Tissue Sarcoma.

The tumor microenvironment of sarcomas has not been studied in detail; in particular, little is known about cancer-associated fibroblasts (CAFs). Sarcoma cells are difficult to distinguish from CAFs, either histomorphologically or immunohistochemically. We scored the expression of individual CAF markers (fibroblast-activating protein [FAP], CD10, and podoplanin) in the intratumoral and marginal areas of 133 sarcomas. We also examined the association between these markers, as well as the number of CD163-positive macrophages (i.e., tumor-associated macrophages), and clinical outcome. In all cases, the log-rank test revealed that those with high marker scores and macrophage counts (except for marginal CD10+ CAFs) showed significantly worse disease-free survival (DFS). Grade 2/3 cases with high CAF scores (excluding the marginal FAP and CD10 scores) showed significantly worse DFS, whereas those with high intratumoral FAP/CD10 and marginal podoplanin scores showed significantly worse metastasis-free survival (MFS), and those with high intratumoral CD10 score showed significantly worse local recurrence-free survival (LFS). Multivariate analysis identified intratumoral CD10/podoplanin scores and marginal FAP/podoplanin scores as independent prognostic factors for DFS, intratumoral FAP/CD10 and marginal FAP/podoplanin/CD163-positive macrophage scores as independent prognostic factors for MFS, and the intratumoral podoplanin score as an independent prognostic factor for LFS. There was a weak-to-moderate correlation between each score and CD163-positive macrophage counts. Patients with high CAF marker expression in the intratumoral and marginal areas have a poorer outcome.

A novel risk classification model integrating CEA, ctDNA, and pTN stage for stage 3 colon cancer: a post hocanalysis of the IDEA-France trial.

We assessed the added value of incorporating carcinoembryonic antigen (CEA) to circulating tumor DNA (ctDNA) and pathological TN (pTN) stage for risk classification in stage 3 colon cancer (CC). We retrospectively analyzed postoperative CEA values in patientswith CC from the IDEA-France phase 3 trial. The relation between disease-free survival (DFS) and CEA was modeled through restricted cubic splines. Prognostic value of CEA, ctDNA, and pTN was assessed with the Kaplan-Meier method. Multivariate analysis was used to identify prognostic and predictive factors for DFS. Among 696 patients (35%), CEA values were retrievable, and for 405 (20%) both CEA and ctDNA were available. An optimized CEA threshold of 2ng/mL was identified, the 3-year DFS was 66.4% for patients above the threshold and 80.9% for those below (HR, 1.74; 95% CI, 1.33-2.28, P < .001). In multivariate analysis, CEA ≥ 2ng/mL contributed significantly to model variability, becoming an independent prognostic factor for DFS (HR, 1.82; 95% CI,1.27-2.59), alongside ctDNA (HR, 1.88; 95% CI, 1.16-3.03) and pTN (HR, 1.78; 95% CI, 1.24-2.54). A novel integrated risk classification combining CEA, ctDNA, and pTN stage reclassified 19.8% of pT4/N2 patients as low risk and 2.5% of pT3/N1 patients as high risk. This new classification demonstrated the 3-year DFS of 80.8% for low-risk patients and 55.4% for high-risk patients (HR, 2.66, 95% CI, 1.84-3.86, P < .001). Postoperative CEA value is a prognostic factor for DFS in stage 3 CC, independently of ctDNA and pTN. It advocates for systematic reporting in future adjuvant trials. Integrating both biomarkers with pTN could refine risk classification in stage 3 CC.

Clinical, pathological and gene expression profiling of estrogen receptor discordance in breast cancer.

Breast cancer (BC) is the world's largest tumor species in which hormone receptor-positive patients have relatively good prognosis. However, majority of patients will develop late resistance, one of the important factors is due to the loss of the original estrogen receptor (ER) expression. We conducted this study in 115 patients with BC who experienced second biopsy at Jiangsu Province Hospital (JSPH) and divided patients into two subgroups ER + to - and ER + to + . First, clinicopathological characteristics between two groups were evaluated. Second, we explored candidate genes related to BC ER intratumor heterogeneity by applying next-generation sequencing (NGS) in 42 patients. Multi-omics integrative analysis of tumor transcriptomic, cancer-related pathway, diagnostic and prognostic value and immune profile were conducted. Besides, preliminary assay were also used to evaluate the correlation between KMT2C and ERα (ESR1) expression. The CCK-8, 5-Ethynyl-2'-deoxyuridine (EdU) assays, Transwell assays and the wound scratch tests were applied to explore the cellular interactions between KMT2C and BC. We find the histological type (p = 0.008) and disease-free survival (DFS) (p = 0.004) were significantly different in two subgroups. In Cox survival analysis, metastasis (Hazard ratio (HR) > 1, p = 0.007) and neo-adjuvant (HR < 1, p < 0.001) are independent prognostic factors of DFS. Besides, by analyzing NGS results, we found four genes KMT2C, FGFR19, FGF1 and FGF4 were highly mutated genes in ER + to - subgroup. Furthermore, the gene KMT2C displayed significant diagnostic value and prognostic value in BC and pan-cancer. In addition, a positive correlation between KMT2C expression and immune infiltrating levels of T cell CD4 + , macrophage and neutrophil was found. In the end, Western blot and RT-qPCR assay were used and found KMT2C and ERα (ESR1) expressions are strongly positive correlated in mRNA and protein level. Inhibition of KMT2C significantly reduced proliferation, invasion, and migration of MCF7 cells. People in two cohorts from JSPH presented different clinical characteristics and prognosis. The gene KMT2C may affect the progression of BC by regulating the molecular, epigenetic activity and immune infiltration. It may also serve as a novel prognostic biomarker for BC patients who underwent ER status converted from positive to negative.

The efficacy of primary progesterone on survival in early breast cancer: A real world scenario.

e12522 Background: Surgery performed during progestogenic milieu improves survival in breast cancer patients. We previously proved efficacy of pre-operative progesterone in high-risk, operable breast cancer. In another multicenter randomized trial, intra-operative peri-tumoral local anesthetic injection showed 29% reduction in mortality. In this study, several patients had also received progesterone injection since this is adopted as standard of care across some centers including ours. We assessed the effectiveness of pre-operative progesterone in patients who were randomized in the local anesthetic study. Methods: We analyzed 1583 patients randomized on the local anesthetic study during December 2011-October 2018 with respect to receipt of progesterone. All patient who had breast lump of ≥2cm and/or node positive were eligible to receive progesterone injection before surgery. Kaplan Meier curves were plotted along with Cox regression analysis to study factors affecting disease-free and overall survival. Results: Of 1583, 454 patients did not receive, and 1129 patients received progesterone before surgery. The median age of whole cohort was 51 years, median pT size was 3 cm, 45% were node positive, 60% ER/PR+ and 24%TNBC. At median follow-up of 68 (0·5-72) months in surviving patients, there were a total of 292 DFS events (progesterone arm-193, no-progesterone arm-99). The 5-year disease-free survival (DFS) was 86.5% in the progesterone arm and 79.2% in the no-progesterone arm (HR-0.57,0.45-0.73, P&lt;0.001). The 5-year overall survival (OS) was 90.5% in the progesterone arm and 82.8% in the no-progesterone arm (HR-0.47,0.36-0.63,P&lt;0.001). On Cox Regression analysis (Table), administration of progesterone injection was an independent prognostic factor for DFS (HR-0.53,0-41-0.70, p&lt;0.001) and OS (HR-0.44,0-32-0.60, p&lt;0.001) both. Conclusions: The receipt of pre-operative progesterone improved outcomes in the setting of another randomized trial. It should be administered to all high risk (T2/N1) breast cancer patients who are planned for surgery first. [Table: see text]

Prognostic significance of HER2 loss after HER2-targeted neoadjuvant treatment in patients with HER2-positive locally advanced breast cancer

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25–30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

The prognostic role of the change in albumin-derived neutrophil-to-lymphocyte ratio during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

The prognosis of patients with locally advanced rectal cancer (LARC) has improved with the adoption of a multidisciplinary treatment approach combining neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME). Developing real-time, sensitive biomarkers to monitor systemic changes during nCRT is of paramount importance. Although the association between albumin-derived neutrophil-to-lymphocyte ratio (Alb-dNLR) and prognosis in various cancers is established, its prognostic value in LARC patients undergoing nCRT is not well-studied. This study enrolled a cohort of 618 LARC patients, stratifying them into two groups according to their change in Alb-dNLR (∆Alb-dNLR) values, using an optimal cut-off point: a low ∆Alb-dNLR group (≤ 0.90) and a high ∆Alb-dNLR group (> 0.90). The prognostic significance of ∆Alb-dNLR was evaluated using a Cox proportional hazards model. The 5-year overall survival (OS) rates were 75.2% in the low ∆Alb-dNLR group (≤ 0.90) and 85.9% in the high ∆Alb-dNLR group (>0.90) (P < 0.001). The 5-year disease-free survival (DFS) rates were 71.2% and 80.6%, respectively (P = 0.016). Multivariate analyses demonstrated that both ∆Alb-dNLR and pre-Alb-dNLR were independent prognostic factors for OS (P ≤ 0.001), while ∆Alb-dNLR was demonstrated as an independent prognostic factor for DFS (P = 0.016). A predictive nomogram, incorporating the ∆Alb-dNLR subgroup, demonstrated enhanced performance (concordance index [C-index] of 0.720 for OS and 0.690 for DFS) compared to the pre-treatment Alb-dNLR subgroup (C-index of 0.700 for OS and of 0.680 for DFS). Therefore, ∆Alb-dNLR shows significant potential as a usable and prognostic biomarker for predicting OS and DFS in LARC patients undergoing nCRT.

Abstract PO4-16-08: Prognostic factors for tumor recurrence after breast-conserving and radiotherapy treatment for early invasive breast cancer: ten years of results in a referral center in Mexico City

Abstract Background: Breast cancer is the most common malignancy in the world, reporting more than 2 million new cases in 2020. In early stages, patients undergo primary surgery. Breast-conserving surgery (BCS) has generally been accepted as a treatment for invasive breast cancer, findings at 20 years still show that lumpectomy and breast irradiation, as compared with mastectomy, have no significant difference in overall survival among the treatment groups. Approximately 10-15% of patients will develop local or systemic recurrence in 5 to 10 years. Factors such as young age (&amp;lt; 45 years), close/positive margins, no breast radiation, are associated with ipsilateral breast tumor recurrence. High grade has been related to distant metastasis. The mortality trend is upward due to a higher incidence of the disease and earlier detection. Methods: This is an observational and retrospective cohort study, which included patients with early breast cancer, who were treated with conserving surgery and received radiotherapy, at the Breast Oncology Service at the UMAE Gineco 4 "Luis Castelazo Ayala" during the period from January 2012 to December 2022. The aim of our study was to describe the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in patients with localized breast cancer treated with BCS. DFS was defined as time from surgery to recurrence event (local recurrence, distant recurrence, contralateral breast cancer, second primary cancer, or death from any cause) whichever occurred first. For statistical analysis, Kaplan Meier and Log-rank methods were used for survival analysis. Cox proportional hazard model was used for multivariate analysis. Results: We included 399 patients, the median follow-up was 88 months (95%CI 86-91). Median age was 59 years. The most common pathological stage was IA in 44.9%, the predominant immunophenotype was luminal A in 56.1% of patients, follow by luminal B in 19.3% and 13% were triple negative. Management of axilla with sentinel node biopsy occurred in 50.1% and 49.9% underwent to lymph node dissection. Regarding surgery outcomes 40.4% of the patients required widening of the margins, 5% of the patients remained with close surgical margins ≤2 mm, 7.5% had complications associated with the surgery, and none related death ocurred. All patients received adjuvant radiotherapy, the median time to initiation was 32 weeks (range 3-70) and 65.4% received adjuvant chemotherapy. Recurrence events occurred in 15.5% of patients, local 2.8%, systemic 8.8%, contralateral breast cancer 1.7%, and second primary 2.2%. Estimated disease-free survival at 5 and 10 years were 86.6% and 74.2%, respectively. In the multivariate analysis independent prognostic factors for DFS were: lobular histology HR 2.95 (95%IC 1.5-5.7), tumor size ≥ 2cm HR 1.95 (95%IC 1.1-3.6), close surgical margins HR 2.62 (95%IC 1-6.6), and ER low expression (1-10%) HR 4.39 (95%CI: 1.6-12.4). Estimated OS at 5 and 10 years for patients who experienced recurrence were 78.4% and 47.4% and for patients without recurrence were 96.8% and 93.5%, respectively (adjusted HR: 10.4, 95%CI: 5.2-20.6). Conclusion: These results suggest that patients with early breast cancer treated with conserving surgery and radiotherapy with risk factors such as lobular carcinoma, tumor size ≥2cm, close margins, and low expression of estrogen receptors have a high risk of recurrence and significantly decreased overall survival at 5 and 10 years. Citation Format: Nayeli Ortega-Avila, Yuly A. Remolina-Bonilla, Janett Caballero-Jasso. Prognostic factors for tumor recurrence after breast-conserving and radiotherapy treatment for early invasive breast cancer: ten years of results in a referral center in Mexico City [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-08.

Abstract PO4-01-08: Co-expression of estrogen receptor (ER), progesterone receptor (PR), and Ki67 in a single breast cancer cell indicates a favorable prognosis in ER-positive breast cancer

Abstract Background: ER-positive breast cancer is biologically and clinically divided into two subtypes: luminal-A and luminal-B. This classification is mainly based on the status of cellular proliferation. At least two different pathways drive cellular proliferation in ER-positive breast cancer. One is a classical pathway where ER binds to estrogen responsive element (ERE), which leads to the expression of downstream molecules, including PR. The other is a non-classical pathway where a complex of ER and relevant factors bind to different sites than ERE. Growth factor signaling has been suggested to potentiate a non-classical pathway. We hypothesized that examining PR status in ER-positive proliferating cells could tell which pathway is more dominant in ER-positive breast cancer. Methods: To test the hypothesis, we used a newly developed triplex immunohistochemistry (IHC) that detects three molecules simultaneously under bright-field microscopy. Postmenopausal patients who were treated with neoadjuvant endocrine therapy with aromatase inhibitors from January 2007 to September 2016 at Saitama Cancer Center were included in this study. ER, PR, and Ki67 expressions were assessed in a single slide using the triplex IHC assay with anti-ER antibody (clone SP1), anti-PR antibody (clone 1E2), and anti-Ki67 antibody (clone 30-9). ER, PR and Ki67 expression was assessed in a single cell nucleus of cancer cells (567 to 4871 cells) from multiple areas in each case. An ER-positive proliferating cell was defined as an ER-positive and Ki67-positive cell. PR status in ER-positive proliferating cells was assessed. When PR was expressed in more than 50% of ER-positive proliferating cells in a clinical case, the tumor was categorized as the PR-positive group. Luminal A and luminal B breast cancers were defined based on the pre-treatment Ki67 labeling index with a cut-off of 14 %. Statistical analyses included the Mann-Whitney test, the log-rank test, and the Cox proportional hazard model. Results: Pre-treatment tissues from 55 patients were evaluated. The median age was 62 (range: 54 to 80) years. The patients were grouped into PR-positive and PR-negative groups. The two groups had no differences in age and pre-treatment T and N stages. The median pre-treatment Ki67 labeling index was 5.9 % in the PR-positive group and 9.9 % in the PR-negative group, which showed a statistically significant difference (P = 0.01). Clinical response to neoadjuvant endocrine therapy was compared, and no difference was observed. The median post-treatment Ki67 labeling index was 3.6 % in the PR-positive group and 13.1 % in the PR-negative group with a significant difference (P = 0.035). The survival was compared between the two groups. The PR-positive group showed a significantly more favorable disease-free survival (DFS) than the PR-negative group (P = 0.0079). To adjust for the background differences including Ki67 and PR status, a multivariate analysis was performed and showed that the PR-positive group had a significantly better DFS than the PR-negative group independent of clinical stage, Ki67 labeling index, and PR status (P = 0.042). Breast cancer-specific survival (BCSS) was also better in the PR-positive group than in the PR-negative group after adjusting for clinical stage, Ki67 labeling index, and PR status (P = 0.043). Interestingly, among patients with luminal A tumors, those in the PR-positive group showed a better DFS than those in the PR-negative group (P = 0.022). Conclusion: PR status in ER-positive proliferating cells was an independent prognostic factor in DFS and BCSS and divided patients with luminal A tumors further into two prognostic groups. Citation Format: Takayuki Ueno, Rie Horii, Hiroshi Matsumoto, Makiko Ono, Yurina Maeshima, Hiroaki Nitta. Co-expression of estrogen receptor (ER), progesterone receptor (PR), and Ki67 in a single breast cancer cell indicates a favorable prognosis in ER-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-08.

Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Clear cell hepatocellular carcinoma: Gd-EOB-DTPA-enhanced MR imaging features and prognosis.

To investigate imaging findings on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and prognosis of clear cell hepatocellular carcinoma (CCHCC) comparing with non-otherwise specified hepatocellular carcinoma (NOS-HCC). The clinical, pathological and MR imaging features of 42 patients with CCHCC and 84 age-matched patients with NOS-HCC were retrospectively analyzed from January 2015 to October 2021. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors for CCHCC. Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier analysis. CCHCC showed fat content more frequently (P < 0.001) and relatively higher Edmondson tumor grade (P = 0.001) compared with NOS-HCC. The lesion-to-muscle ratio (LMR) and lesion-to-liver ratio (LLR) of CCHCC on pre-enhancement T1-weighted imaging (pre-T1WI) (P = 0.001, P = 0.003) and hepatobiliary phase (HBP) (P = 0.007, P = 0.048) were significantly higher than those of NOS-HCC. The area under the curve (AUC) for fat content, LLR on pre-T1WI and their combination with better diagnostic performance in predicting CCHCC were 0.678, 0.666, and 0.750, respectively. There was no statistically significant difference in clinical outcomes between CCHCC and NOS-HCC. Multivariate Cox analysis confirmed that tumor size > 2cm and enhancing capsule were independent prognostic factors for DFS and OS among CCHCC patients. Fat content and adjusted lesion signal intensity on pre-T1WI and HBP could be used to differentiate CCHCC from NOS-HCC. CCHCC had similar prognosis with NOS-HCC.

The Effect of Age on Pancreaticoduodenectomy; Comorbidities, Short-term Outcomes, and Survival.

To evaluate the complications, mortality, and survival rates of patients aged >70 years undergoing pancreaticoduodenectomy, and to determine associated risk factors. Descriptive study. Place and Duration of the Study: General Surgery Clinic of Eskişehir Osmangazi University Medical Faculty Hospital, Eskişehir, Turkiye, from January 2014 to September 2020. A retrospective scrutiny of 94 patients who had undergone pancreaticodueodenectomy, was carried out. The patients were separated into two age groups of younger and older than 70 years, and were compared in respect of clinicopathological characteristics, comorbidities, perioperative characteristics, and complications. Independent risk factors for the endpoints of perioperative mortality and survival were investigated. No significant difference was determined between the groups in respect of biochemical values, and perioperative and histochemical characteristics. Comorbidities were present at a higher rate in the older patients (77.8% vs. 38.8%, p<0.001). The postoperative complication rates were similar (33.3% vs. 32.7%, p=0.944). Perioperative mortality (first 30 days) was determined at a significantly higher rate in the older age group (20.0% vs. 4.1%, p=0.016). The age of patients >70 years increased the risk of mortality 4.851-fold but was not an independent predictive factor (p=0.086). The groups were similar in respect of disease-free survival (DFS) and overall survival (OS, Log-rank p=0.780, p=0.386). Age [Hazard Ratio (HR): 1.029, p=0.048] and pancreas adenocarcinoma (HR: 1.846, p=0.028) were determined to be independent prognostic factors for DFS, and pancreas adenocarcinoma (HR 1.940, p=0.023) for OS. Older age was not seen to change survival in patients undergoing pancreaticoduodenectomy, but mortality within the first 30 days was affected. Age is not accepted as an absolute contraindication. It is recommended that pancreaticoduodenectomy is performed on patients aged >70 years with careful patient selection, prudent preoperative preparation, a meticulous surgical technique, and close multidisciplinary postoperative support. Pancreaticoduodenectomy, Elderly, Comorbidity, Complication, Mortality, Survival.

Platinum-based neoadjuvant chemotherapy upregulates STING/IFN pathway expression and promotes TILs infiltration in NSCLC.

To evaluate the effects of platinum-based neoadjuvant chemotherapy (NACT) on the STING/IFN pathway and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC), as well as clinicopathological factors affecting patient survival. A total of 68 patients aged 34-77 years with NSCLC who received neoadjuvant chemotherapy and surgical treatment from March 2012 to February 2019 were reviewed, and the clinical pathological data and paired tissue specimens before and after NACT were collected. Immunohistochemistry and immunofluorescence were used to detect the protein levels of STING, PD-L1 and IFN-β, and the infiltration density of CD3+ TILs and CD8+TILs. The correlation between the expression of STING, PD-L1, IFN-β and the infiltration density of CD3+ TILs and CD8+ TILs as well as the clinicopathological characteristics before and after NACT was analyzed. The relationship between the related indexes, clinicopathological features and prognosis was also discussed. NACT increased the expression of STING, IFN-β and PD-L1 in tumor cells, and the infiltration of CD3+ and CD8+ TILs. In addition, ypTNM stage, ypN stage, changes in CD3+ TILs and in PD-L1 were associated with DFS (disease-free survival). CD3+ TILs changes and ypN stage were associated with OS (overall survival). Notably, ypN stage and CD3+ TILs changes were independent prognostic factors for DFS and OS. NACT stimulates STING/IFN-β pathway, promotes infiltration of CD3+ and CD8+ TILs, triggers innate and adaptive immunity, and also upregulates PD-L1, which complemented the rationale for neoadjuvant chemotherapy in combination with immunotherapy. In addition, DFS was longer in patients with ypTNM I, ypN0-1, and elevated CD3+TILs after NACT. Patients with ypN0 and elevated CD3+ TILs after NACT had better OS benefits.

Treatment patterns and clinical outcomes of patients with resectable non–small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World)

BackgroundNeoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non–small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. MethodsNeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. ResultsA total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. ConclusionsThe study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

Oncologic Outcome of Patients With Pathologic T0 Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

To investigate the oncologic outcomes of patients with esophageal squamous cell carcinoma (ESCC) who have achieved a pathologic complete response (pCR) of the primary tumor (ypT0) after neoadjuvant chemoradiotherapy (NCRT). Patients with thoracic ESCC who underwent scheduled NCRT followed by surgery at our hospital between January 2010 and December 2022 were retrospectively analyzed. Only patients with ypT0 disease were enrolled in this study. A total of 118 patients were ultimately enrolled in this study. Ninety-two patients achieved pCR in the primary tumor and lymph nodes (ypT0N0), while 26 patients had residual metastatic disease in 52 lymph nodes (ypT0N+). Forty-five of the 52 lymph nodes with residual tumors were abdominal lymph nodes. Positive lymph nodes were more often observed in patients with tumors located in the lower third of the esophagus. The 1-, 3-, and 5-year overall survival (OS) rates for the entire study group were 96.5%, 79.5%, and 77.1%, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 90.5%, 76.8%, and 69.0%, respectively. According to multivariate analyses, pN classification was an independent predictor of both OS and DFS (P < 0.05), while sex and cT classification were also found to be independent prognostic factors for DFS (P < 0.05). Residual nodal metastatic disease in patients with ypT0 ESCC after NCRT was more often found in the abdominal lymph nodes. pN classification was an independent predictor of both OS and DFS for ypT0 ESCC patients after NCRT.

The impact of neo/adjuvant treatment choices on prognosis for surgically treated small-cell neuroendocrine carcinoma of the cervix.

Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.

Combination of DNA ploidy, stroma, and nucleotyping predicting prognosis and tailoring adjuvant chemotherapy duration in stage III colon cancer.

DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy. This study aimed to validate PSN's prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration. A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020. Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan-Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity. Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% versus 83.62% versus 79.80%, p = 0.029; OS: 96.69% versus 93.99% versus 90.12%, p = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002-1.981, p = 0.049] and OS (HR = 1.720, 95% CI: 1.127-2.624, p = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 versus 0.553, p = 0.020) and 10-year (0.694 versus 0.532, p = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% versus 71.52%, p = 0.026; OS: 96.77% versus 85.46%, p = 0.007). The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination.