Prolonged Disease-free Survival Research Articles

Influence of brain metastases on the classification, treatment, and outcome of patients with extracranial oligometastasis: a single-center cross-sectional analysis

Background and introductionIncreasing evidence suggests that a subgroup of patients with oligometastatic cancer might achieve a prolonged disease-free survival through local therapy for all active cancer lesions. Our aims are to investigate the impact of brain metastases on the classification, treatment, and outcome in these patients.Materials and methodsWe analyzed a total of 7,000 oncological positron emission tomography scans to identify patients with extracranial oligometastatic disease (defined as ≤ 5 intra- or extra-cranial metastases). Concurrent magnetic resonance imaging brain was assessed to quantify intracranial tumor burden. We investigated the impact of brain metastases on oligometastatic disease state, therapeutic approaches, and outcome. Predictors for transitioning from oligo- to polymetastatic states were evaluated using regression analysis.ResultsA total of 106 patients with extracranial oligometastases and simultaneous brain metastases were identified, primarily originating from skin or lung/pleura cancers (90%, n = 96). Brain metastases caused a transition from an extracranial oligometastatic to a whole-body polymetastatic state in 45% (n = 48) of patients. While oligometastatic patients received systemic therapy (55% vs. 35%) more frequently and radiotherapy for brain metastases was more often prescribed to polymetastatic patients (44% vs. 26%), the therapeutic approach did not differ systematically between both sub-groups. The oligometastatic sub-group had a median overall survival of 28 months compared to 10 months in the polymetastatic sub-group (p < 0.01).ConclusionIn patients with brain metastases, a low total tumor burden with an oligometastatic disease state remained a significant prognostic factor for overall survival. Presence of brain metastases should therefore not serve as exclusion criterion for clinical trials in the field of oligometastatic disease. Moreover, it underscores the importance of considering a multimodality treatment strategy in oligometastatic cancer patients.

Cost-effectiveness of pembrolizumab as an adjuvant treatment of renal cell carcinoma post-nephrectomy in Switzerland

Aims Pembrolizumab has demonstrated significantly prolonged disease-free survival and overall survival (OS) among adult patients post-nephrectomy who have an intermediate-high risk, high-risk, or M1 stage with no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component. The aim of this study was to evaluate the cost-effectiveness of pembrolizumab for patients with RCC post-nephrectomy versus observation in Switzerland. Materials and methods A previously published Markov model was adapted for the Swiss setting to estimate the cost-effectiveness of adjuvant pembrolizumab versus observation from the Swiss statutory health insurance perspective. Transition probabilities between model states were estimated using survival curves from KEYNOTE-564 (data cut-off: June 14, 2021). Outcomes included costs (2022 Swiss francs [CHF]), quality-adjusted life-years (QALYs), and life-years (LYs), measured over a lifetime horizon. Costs included drug acquisition and administration for adjuvant and subsequent therapy. Both costs and effectiveness were discounted at 3.0% annually. Cost-effectiveness was evaluated at a hypothetical willingness-to-pay (WTP) threshold of CHF 100,000 Sensitivity was assessed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. Results Over a lifetime horizon, the total incremental cost for pembrolizumab versus observation was CHF 59,089, providing incremental gains of 0.90 QALYs (1.07 LYs); the incremental cost-effectiveness ratio was CHF 65,299/QALY. Pembrolizumab was deemed cost-effective versus observation, with a 69.9% probability of cost-effectiveness. Limitations A more recent interim analysis data cut from KEYNOTE-564 with median follow up of 57.2 months has since been published; however, these were not available at the time of analysis. It would likely have minimal impact on transition probabilities from disease-free, and the current approach remains conservative for predicting OS for pembrolizumab. Conclusions As an adjuvant treatment of RCC post-nephrectomy, pembrolizumab was found to be cost-effective versus observation in Switzerland at a WTP threshold of CHF 100,000/QALY. Policy makers should consider pembrolizumab as an adjuvant treatment for patients with RCC post-nephrectomy when making decisions regarding resource allocation.

Enhanced patient journey associated with improved overall survival in colon cancer patients: A study by the Ligurian Oncology Network.

Colon cancer imposes a significant burden on global healthcare systems, necessitating efforts to improve oncology care quality and patient outcomes. We studied the correlation between care quality and survival outcomes among colon cancer patients within the Ligurian Oncology Network (Italy). We developed an Overall Quality Score (OQS) to evaluate the impact of oncology care quality on survival outcomes within the Ligurian Oncology Network. OQS indicators were selected through expert consensus, covering screening, diagnosis, treatment, and follow-up. A sample of colon cancer patients diagnosed in 2012 was randomly selected from administrative healthcare data. Analyses were performed using two models: a binary model (High and Low OQS) and a stratified model (Low, Medium, and High OQS). Statistical analysis involved survival curves, log-rank tests, and Cox proportional hazards models using SAS 9.4. Of 175 eligible colon cancer patients, 150 were included. Following a median follow-up of 7.6 years, a correlation between High-OQS (⩾ 65%) and prolonged disease-free survival was observed (unadjusted HR 0.57, 95%CI 0.33-0.99, log-rank p=0.041). The five-year disease-free survival rate for High-OQS patients was 70% (95%CI 57-80%), compared to 53% (95%CI 41-64%) for Low-OQS patients. Similarly, the five-year overall survival rate was 78% (95%CI 65-86%) for High-OQS patients, compared to 58% (95%CI 45-68%) for Low-OQS patients (unadjusted HR 0.56, 95%CI 0.31-1.00, log-rank p=0.048). Our findings highlight the potential impact of the patient journey on colon cancer survival outcomes. Optimising care pathways might improve patient outcomes in colon cancer management.

The many faces of autoimmune-mediated melanocyte destruction in melanoma.

Melanoma is the most severe form of skin cancer with an incidence that is increasing all over the world. Melanoma cells derive from normal melanocytes and share different melanocyte-specific antigens, the same antigens against which an immune reaction develops in vitiligo, a skin disease characterized by autoimmune-mediated melanocyte destruction. The purpose of this review is to present the autoimmune-mediated melanocyte destruction associated with melanoma development, progression and treatment. Patients with vitiligo seem to have a lower chance of developing melanoma. On the other hand, patients with melanoma can develop depigmented lesions even at distant sites from the primary tumor, defined as melanoma-associated leukoderma (MAL). Drug-associated leukoderma (DAL) was also described in melanoma patients treated with immunotherapy or targeted therapy and it seems to be a favorable prognostic factor. Clinically, MAL and DAL can be diagnosed as vitiligo and there are few differences between these three entities. In this review, the incidence of DAL in melanoma patients treated with different therapies was researched in the literature and patient outcome was recorded, with studies showing a prolonged disease-free survival in melanoma patients with DAL, treated with immune checkpoint inhibitors. Further studies are however needed to understand the dynamics of autoimmune-mediated melanocyte destruction.

Tertiary lymphoid structures' pattern and prognostic value in primary adenocarcinoma of jejunum and ileum.

To date, there have been no reports on tertiary lymphoid structures (TLS) in primary adenocarcinoma of jejunum and ileum. In this study, we employed digital pathology image analysis software to classify and quantify TLS, and evaluated the maturity of TLS using immunohistochemistry. Molecular genetics and immunotherapy biomarker detection were performed using next-generation sequencing technology, such as tumor mutational burden (TMB) and microsatellite instability (MSI). The aim of this study was to investigate the presence, location, maturity, association with immunotherapy biomarkers, and prognostic value of TLS in primary adenocarcinoma of jejunum and ileum. Compared to secondary follicle-like TLS (SFL-TLS), intra-tumoral TLS (IT-TLS) were more likely to manifest as early TLS (E-TLS) (P = 0.007). Compared to IT-TLS, SFL-TLS had a higher propensity to occur at the invasive margin(IM) (P = 0.032) and showed a trend towards being more prevalent at the tumor periphery (P = 0.057). In terms of immunotherapy biomarkers, there was a higher trend of IM-TLS density in PD-L1(22C3) score CPS < 1 group compared to PD-L1(22C3) score CPS ≥ 1 group (P = 0.071). TMB-H was significantly associated with MSI-H (P = 0.040). Univariate survival analysis demonstrated a correlation between high SFL-TLS group and prolonged disease free survival (DFS) (P = 0.047). There was also a trend towards prolonged DFS in the E-TLS-high group compared to the E-TLS-low group (P = 0.069). The peri-tumoral TLS (PT-TLS)-high group showed a trend of prolonged overall survival (OS) compared to the PT-TLS-low group (P = 0.090). In conclusion, the majority of TLS were located at the invasive margin and tumor periphery, predominantly consisting of mature TLS, while IT-TLS were mainly immature. Notably, TMB was closely associated with MSI and PD-L1, indicating potential predictive value for immunotherapy in primary adenocarcinoma of jejunum and ileum.

CD8-Positive T-Cells Are Key Immune Cells for Predicting the Therapeutic Effect of Neoadjuvant Chemotherapy in Triple-negative Breast Cancer.

Patients with triple-negative breast cancer (TNBC) who obtain a pathological complete response (pCR) after neoadjuvant chemotherapy have an improved prognosis. Lymphocyte-predominant breast cancer is more likely to respond to neoadjuvant chemotherapy. Here, we investigated the correlation between tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsy specimens from patients with TNBC in relation to response to NAC. The level of infiltration by immune cells expressing immune cell lineage surface markers (CD8, CD4, CD19, CD14, CD11c, and CD11b) in biopsy specimens from 52 patients with TNBC was examined using multispectral immunofluorescent labelling. The level of CD8-positive TILs was significantly higher in patients with a pCR (p=0.045). The Cox proportional hazard model confirmed that lymph node involvement was associated with poorer disease-free survival (p=0.008). A high level of CD8-positive TILs was related to significantly prolonged disease-free survival in patients with node-positive TNBC (p=0.018). Assessing infiltration by CD8-positive TILs in the primary tumor is a useful biomarker to predict pCR and improved outcome in patients with node-positive TNBC.

SCGB1A1 as a novel biomarker and promising therapeutic target for the management of HNSCC.

Head and neck cancer (HNC) is the sixth most common type of cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) accounts for 90% of HNC cases. Furthermore, HNSCC accounts for 400,000 cancer-associated deaths worldwide each year. However, at present there is an absence of a versatile biomarker that can be used for diagnosis, prognosis evaluation and as a therapeutic target for HNSCC. In the present study, bioinformatics analysis was used to assess the relationship between hub genes and the clinical features of patients with HNSCC. The findings from the bioinformatics analysis were then verified using clinical samples and in vitro experiments. A total of 51 overlapping genes were identified from the intersection of differentially expressed genes and co-expressed genes. The top 10 hub genes were obtained from a protein-protein interaction network of overlapping genes. Among the hub genes, only secretoglobin family 1A member 1 (SCGB1A1) was significantly associated with both overall and disease-free survival. Specifically, upregulated SCGB1A1 expression levels were associated with prolonged overall and disease-free survival. Moreover, the SCGB1A1 expression levels were negatively correlated with drug sensitivity. Notably, it was demonstrated that SCGB1A1 was involved in tumor immunoreaction by affecting the infiltration of cells and checkpoint regulation of immune cells. Additionally, it was shown that SCGB1A1 regulated multiple key cancer-related signaling pathways, including extracellular matrix receptor interaction, transforming growth factor-β and tumor metabolism signaling pathways. Based on the results of the present study, SCGB1A1 may serve as a novel biomarker for predicting the diagnosis, prognosis and therapeutic effectiveness of certain drugs in patients with HNSCC. Moreover, SCGB1A1 may serve as a potential therapeutic target for the management of HNSCC.

Searching For Ideal Definite Treatment of Sinonasal Squamous Cell Carcinoma with Orbit Invasions.

Sinonasal squamous cell carcinoma (SqCC) often invades the orbit. Treatment of sinonasal cancer invading orbit can vary depending on the medical center and the extent of the invasion. The definitive treatment strategy, whether it involves preserving the orbit or not, varies on a case-by-case basis and leads to different outcomes. Currently, a multimodal treatment approach, which includes surgery, chemotherapy (CTx), radiotherapy (RT), or concurrent chemoradiotherapy (CCRT), is frequently employed for sinonasal cancers. This study aims to evaluate the prognosis of sinonasal SqCC with orbit invasion in various perspectives. We conducted a retrospective review of patients with primary sinonasal SqCC invading the orbit who were treated at between 2009 and 2018. We examined factors such as the extent of tumor, orbit invasion, treatment strategies, recurrence rates, and survival rates. Overall survival (OS) and disease-free survival (DFS) rates did not significantly differ based on the grade of orbit invasion. When tumor resection with orbit preservation was performed as definitive treatment, DFS was significantly longer compared to cases where surgery was not the definitive treatment (RT, CCRT). There was no significant difference in DFS between those who underwent orbit exenteration and those who underwent tumor resection with orbit preservation as the definitive treatment. Tumor resection with orbit preservation as the definitive treatment appears to be the preferred approach, leading to prolonged DFS while ensuring survival in cases of SqCC with orbit invasion.

Outcomes of De Novo Oligometastatic Breast Cancer Treated With Surgery of Primary and Metastasis Directed Radiotherapy.

With sensitive imaging for breast cancer, the question arises whether present-day oncologists treat dOMBC with palliative systemic therapy (ST), which, a few years earlier, would have been treated with curative intent. We retrospectively analyzed outcomes of dOMBC treated with curative intent using a combination of surgery, metastasis-directed radiotherapy (RT), and adjuvant/neoadjuvant ST and have also explored the possible role of total lesional glycolysis of metastases and p53 immunohistochemistry in predicting outcomes. Data were collected from a prospectively maintained database using electronic medical records and Radiation Oncology Information System. In the study, dOMBC was defined as up to 3 metastatic sites, all amenable to treatment with ablative RT and primary and axillary disease amenable to curative surgery. Patients were treated with surgery, ST, and RT. Patients underwent either breast conservation surgery or modified radical mastectomy. Patients were treated with 6 to 8 cycles of chemotherapy in the neoadjuvant and/or adjuvant setting. Hormone receptor-positive patients received either tamoxifen or aromatase inhibitors. Trastuzumab was offered to Her-2-neu receptor-positive patients. RT included locoregional RT and metastases-directed ablative body RT. The median progression-free survival was 39 months (95% CI: -28.7 to 50.1mo). Two and 3 year estimated disease-free survival (DFS) was 79% and 60.5%, respectively. The median overall survival was not reached. The estimated 3-year overall survival was 87.3%. Total lesional glycolysis of metastases score and p53 status did not affect DFS. Combination treatment of surgery, metastases-directed ablative RT, and ST may provide prolonged DFS in dOMBC.

A retrospective study of adjuvant albumin-bound paclitaxel plus S-1 after D2 gastrectomy versus oxaliplatin plus S-1 in gastric cancer

Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1–14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.

Quality of lymph node dissection and early recurrence in robotic versus thoracoscopic lobectomy for stage N1-2 non-small cell lung cancer: Eleven-year real-world data from a high-volume center

BackgroundThe efficacy of lymph node dissection (LND) and oncological outcomes of robot-assisted (RL) versus video-assisted thoracoscopic lobectomy (VL) for non-small cell lung cancer (NSCLC) with nodal involvement remains controversial. This study aims to compare LND quality and early recurrence (ER) rate between RL and VL for stage N1-2 NSCLC patients based on eleven-year real-world data from a high-volume center. MethodsPathologic stage IIB-IIIB (T1-3N1-2) NSCLC patients undergoing RL or VL in Shanghai Chest Hospital from 2010 to 2021 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM, 1:4 RL versus VL) was performed to mitigate baseline differences. LND quality was evaluated by adequate (≥16) LND and nodal upstaging rates. ER was defined as recurrence occurring within 24 months post-surgery. ResultsOut of 1578 cases reviewed, PSM yielded 200 RL and 800 VL cases. Without compromising perioperative outcomes, RL assessed more N1 and N2 LNs and N1 stations, and led to higher incidences of adequate LND (58.5 % vs. 42.0 %, p < 0.001) and nodal upstaging (p = 0.026), compared to VL. Notably, RL improved perioperative outcomes for patients undergoing adequate LND than VL. Finally, RL notably reduced ER rate (22.0 % vs. 29.6 %, p = 0.032), especially LN ER rate (15.0 % vs. 21.5 %, p = 0.041), and prolonged disease-free survival (DFS; hazard ratio = 0.837, p = 0.040) compared with VL. Further subgroup analysis of ER and DFS within the cN1-2-stage cohort verified this survival benefit. ConclusionsRL surpasses VL in enhancing LND quality, reducing ER rates, and improving perioperative outcomes when adequate LND is performed for stage N1-2 NSCLC patients.

Ki67 is a better marker than PRAME in risk stratification of BAP1-positive and BAP1-loss uveal melanomas

BackgroundAccurate risk stratification of uveal melanoma (UM) patients is important for determining the interval and frequency of surveillance. Loss of BAP1 expression has been shown to be strongly associated with...

Efficacy and safety of bevacizumab and platinum‑based chemotherapy as neoadjuvant regimen for stage‑IIIA non‑squamous non‑small cell lung cancer: A retrospective study.

Bevacizumab plus platinum-based chemotherapy provides modest benefits in non-squamous non-small cell lung cancer (NSCLC), while its application as a neoadjuvant regimen has yet to be validated. The present study aimed to assess the efficacy of neoadjuvant bevacizumab plus platinum-based chemotherapy in patients with stage-IIIA non-squamous NSCLC. Data from 110 patients with stage-IIIA non-squamous NSCLC with negative driver genes, who received neoadjuvant bevacizumab plus platinum-based chemotherapy (n=50) or neoadjuvant platinum-based chemotherapy alone (n=60), and tumor resection, were retrospectively reviewed in the current study. In addition, the data on pathological response, disease-free survival (DFS), overall survival (OS) and adverse events were obtained. The results demonstrated that neoadjuvant bevacizumab plus chemotherapy did not significantly increase the pathological complete response (pCR) rate in comparison with neoadjuvant chemotherapy alone (18.0 vs. 8.3%; P=0.130). However, neoadjuvant bevacizumab plus chemotherapy significantly increased the rates of DFS (P=0.007) and OS (P=0.049) compared with neoadjuvant chemotherapy alone. Adjustments were then performed using multivariate logistic or Cox regression analyses, which demonstrated that neoadjuvant bevacizumab plus chemotherapy in comparison with neoadjuvant chemotherapy alone only significantly independently prolonged DFS [hazard ratio (HR)=0.251; P=0.042], but did not significantly affect pCR (odds ratio=2.897; P=0.117) or OS (HR=0.297; P=0.158). Furthermore, no significant differences were demonstrated between the number of adverse events in patients receiving neoadjuvant bevacizumab plus chemotherapy in comparison with those receiving neoadjuvant chemotherapy alone (all P>0.05). In conclusion, neoadjuvant bevacizumab plus platinum-based chemotherapy was only associated with a significant improvement in the rate of DFS, but showed limited efficacy in improving pCR and OS rates in comparison with neoadjuvant chemotherapy alone in patients with stage-IIIA non-squamous NSCLC. Therefore, a larger sample size and randomized controlled studies are needed for further validation of the findings of the present study.

Benefits of adjuvant treatment with the Pingxiao capsule in patients with early breast cancer: A single‑center retrospective cohort study.

Early breast cancer (EBC) is cancer that has not spread beyond the breast or the axillary lymph nodes. The present retrospective cohort study investigated the efficacy and safety of the Pingxiao capsule (PXC), which contains a formula of traditional Chinese herbs, as adjuvant therapy in patients with EBC in a single Chinese academic medical center. Patients with EBC who had received surgery and chemotherapy were analyzed and divided into the PXC and non-PXC groups. Disease-free survival (DFS) time, overall survival (OS) time, demographic characteristics and adverse events were examined. Kaplan-Meier survival curves were used to compare the differences in DFS and OS. A total of 371 participants with a median age of 54 years were included in this study. The median DFS time of all patients was 101 months. The overall DFS rate was 72.1% in the PXC group compared with 63.6% in the non-PXC group. For women with hormone receptor-negative tumors, the DFS rate in the PXC group was significantly higher than that in the non-PXC group, irrespective of node status. Adjuvant treatment with PXC for ≥3 months was associated with significantly longer median DFS time compared with that in the non-PXC group. In addition, the incidence of neutropenia rated to be grade 2 or higher was significantly lower in the PXC group compared with that in the control group, and a markedly, but non-significantly, lower prevalence of nausea was observed in PXC group (0 vs. 4.1%). In conclusion, PXC as an adjuvant therapy along with chemotherapy is associated with prolonged DFS times in patients with EBC when compared with chemotherapy alone. The therapeutic value of combined PXC and systemic chemotherapy should be further elucidated by rigorous prospective clinical trials.

EGFR-TKI as neoadjuvant treatment in patients with NSCLC with EGFR sensitive mutation: A retrospective real-world analysis.

8081 Background: This study aimed to evaluate the efficacy and outcome of Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as preoperative neoadjuvant treatment in patients with NSCLC and EGFR sensitive mutation. Methods: A retrospective analysis was conducted. Patients with resectable stage I-III NSCLCs and received neoadjuvant treatment with any generation of EGFR-TKI before surgical resection were enrolled. The primary endpoint were major pathological response (MPR) and objective response rate (ORR), the second endpoints included diseases down staging, surgical outcomes, disease-free survival (DFS) and overall survival (OS). Results: A total of 58 patients were enrolled. Female accounted for 62.1% and most of them (77.6%) were never-smoker. Forty-five (77.6%) patients received the first generation of EGFR-TKI and 11 received the third. The median duration of EGFR-TKI before surgery was 3.6 months (0.7-19.5m). Nine (15.5%) patients achieved MPR and one patient (1.71%) achieved pathological complete response (pCR). The ORR was 60.3% (35/58) according to RECIST v1.1. Eighteen patients achieved TNM downstaging with T downstaging occurred in 44.8% of patients and N downstaging was about 32.8%. Majority of patients (96.6%) underwent thoracoscopic surgery and the rate of R0 resection was 82.8% (48/58). The DFS and OS of the whole cohort was 25.7months and not reached respectively. Patients with MPR had statistically improved outcomes than those without. What noticeable was that patients with tumor regression grade 3 (13/58) (residual viable tumor cells counts for 10% to 50%) also demonstrated a significant benefit from EGFR-TKI preoperative treatment than those with TRG4 or 5 (residual viable tumor cells&gt;50%) (p = 0.01). We define patients with TRG1 to TRG3 as deep pathological regression (DPR) and the rest as non-DPR, and the DPR cohort showed significantly prolonged DFS than those with non-DPR (median DFS, 60.9 vs 16.7 months; HR, 0.29 (95%CI: 0.11-0.74), p = 0.006), the data of OS was not mature. Subgroup analysis validated DPR was an independent predictive factor for DFS. Conclusions: EGFR-TKI as neoadjuvant therapy had good effect on tumor pathological regression and disease downstaging, DPR patients were more likely to achieve long-term disease-free survival. Patients with NDPR should be closely followed up and appropriate adjuvant therapy was necessary after surgery due to the high risk of reccurence.

High PLK3 levels are linked with less tumor invasion, lower FIGO stage and better prognosis of endometrial cancer.

Aim: To evaluate correlations of tumor PLK3with clinical features and prognosis of resectable endometrial cancer (EC) patients.Methods: Tumor tissues from 200 EC patients receiving surgical resections and adjacent tissues from 50 of them were collected for PLK3 determination using immunohistochemistry.Results: Tumor PLK3 negatively linked with myometrial invasion ≥50%, lymphovascular invasion, stromal cervical invasion, and International Federation of Gynecology and Obstetrics stage (all p <0.050). High tumor PLK3 independently related to longer disease-free survival (DFS) (p=0.044) and overall survival (OS) (p=0.049). Its prognostic value was also validated by time-dependent receiver operating characteristic analyses (area under curve at most timepoints was >0.700).Conclusion: Tumor PLK3 potentially reflects prolonged DFS and OS in EC patients undergoing surgical resections.

Adjuvant chemotherapy for stage II and III gastric adenocarcinoma: A retrospective analysis with long-term follow-up

BackgroundWhether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown. MethodsWe retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone. ResultsThe median age of patients was 67.0 (range 24.6 – 98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease. ConclusionAlthough fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer.

Association of Preoperative and Postoperative Plasma Syndecan-1 and Colorectal Cancer Outcome.

A three-dimensional network constructed using glycocalyx (GCX) extends throughout the cancer cell nest in human colorectal cancer (CRC). GCX was found to be closely related to cancer. We examined the prognostic correlation and potential of syndecan-1 (SDC1), a representative proteoglycan of GCX, as a biomarker. We analyzed SDC1 in the transcriptomic profiles of a major publicly available CRC cohort from The Cancer Genome Atlas (TCGA) using a computational algorithm. We investigated serum SDC1 levels preoperatively and on postoperative day seven in 48 patients with stage I-III CRC who underwent surgery during July-December 2019 at Gifu University Hospital. For TCGA, no significant differences existed between the high and low SDC1 expression groups regarding disease-free, disease-specific, and overall survival for stage I-III, and only overall survival for stage IV was significantly different. In our study, among the 48 patients, 17 (no recurrence), 13 (1 recurrence), and 18 (10 recurrences) had stage I-III, respectively. Preoperative and postoperative day 7 SDC1 levels for patients with stage I-III were 10.7±2.3 and 9.9±3.1 ng/ml (p=0.40), 11.1±1.7 and 10.1±0.8 ng/ml (p=0.07), and 10.3±2.0 and 9.5±1.4 ng/ml (p=0.15), respectively. In stage II and III, patients were divided into two groups according to differences between preoperative and postoperative SDC1 levels (SDC1pre-pro). SDC1pre-pro ≤0 group significantly prolonged disease-free survival compared with SDC1pre-pro >0 group (p=0.048). Dynamic change in serum SDC1 levels serves as a prognostic biomarker for stage II and III colorectal cancer.

Abstract 3650: Deep learning-based image cytometry and co-localization index in tumor immune microenvironment

Abstract Background: In pathology, digitizing tissue slides has prompted a remarkable development in image analysis using deep learning. This technological advancement is anticipated to aid in pathological diagnosis and to enhance patient management. Deep learning-based image cytometry (DL-IC) enables accurate cell identification and counting and the acquisition of vast amounts of location information from tissue slides. DL-IC can capture information about the diverse and complex tumor immune microenvironment(TIME) and its constituent cells and help identify biomarkers to predict patient treatment efficacy and prognosis. This study will introduce a spatial interaction map and co-localization index (CLI) for the analysis of TIME using DL-IC. Materials and Methods: Cu-Cyto, a deep learning-based image analysis technology, was used in this study; bit-pattern kernel filtering technology, which can accurately count cells while avoiding the determination of multiple cell counts, was used by Cu-Cyto (Abe T, et al. Anticancer Res. 43:3755, 2023). First, the accuracy of cell counting using Cu-Cyto was evaluated. Second, tumor tissue slides with immunohistochemical (IHC) and hematoxylin-eosin (H&amp;E) staining were prepared from surgical specimens of patients with rectal cancer who had undergone neoadjuvant chemoradiotherapy (NACRT), and the relationship between the co-localization index (CLI) of cancer cells and CD8+T cells and prognosis was investigated. CLI was defined to predict cell- cell interactions on the basis of the relative distances between different cell types (Nagasaka T. PCT/JP 2021/021455). Results: The performances of three versions of Cu-Cyto were evaluated according to their learning stages. In the early stage of learning, the F1 score for immunostained CD8+ T cells (0.343) was higher than that for non-immunostained cells (adenocarcinoma cells [0.040] and lymphocytes [0.002]). In the latest stage of learning, the F1 scores for adenocarcinoma cells, lymphocytes, and CD8+ T cells were 0.589, 0.889, and 0.911, respectively. Next, we examined the correlation of CLI between cancer cells and CD8+ T cells with prognosis: patients with a higher CLI significantly prolonged five-year disease-free survival (P=0.038), while there was no substantial difference in five-year overall survival (P=0.57). Conclusion]: Cu-Cyto performed well in cell determination. In particular, IHC was able to increase the learning efficiencies in the early stages of learning. The CLI calculated using Cu-Cyto ts an objective, reproducible, and innovative quantitative approach for assessing cell-cell interactions, which has been shown to be associated with recurrence-free survival in patients with rectal cancer after NACRT. Its performance is expected to improve even further with continuous learning, and the DL-IC can contribute to the implementation of precision oncology. Citation Format: Tomoki Abe, Kimihiro Yamashita, Toru Nagasaka, Tomosuke Mukoyama, Souichirou Miyake, Yasuhiro Ueda, Masayuki Ando, Yuki Okazoe, Takao Tsuneki, Yukari Adachi, Ryunosuke Konaka, Ryuichiro Sawada, Hironobu Goto, Hiroshi Hasegawa, Shingo Kanaji, Takeru Matsuda, Takumi Fukumoto, Yoshihiro Kakeji. Deep learning-based image cytometry and co-localization index in tumor immune microenvironment [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 3650.

Critical appraisal of surgical margins according to KRAS status in liver resection for colorectal liver metastases: Should surgical strategy be influenced by tumor biology?

BackgroundKRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status. MethodsAll patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival. ResultsThe analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01–2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06–1.91). ConclusionsKRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.