Recurrence In Cancer Patients Research Articles

Effectiveness of principal component analysis in breast cancer diagnosis: An empirical and visualization analysis

With the development of computer science technology, it is increasingly common to apply computer science technology to the medical field, and one of the typical examples is to predict the probability of cancer cells recurrence in cancer patients. However, there is still a lack of unified explanation for the impact of the principal component analysis (PCA) dimensionality reduction method used in prediction on the final experimental results. Therefore, the research topic of this paper is the effect of PCA dimensionality reduction method on the accuracy of cancer prediction. The methodology in this paper is as follows: First, patient data were collected, based on a usable machine learning repositor. It has 569 instances, which contains both malignant and benign tumors. Second, exploratory data analysis is performed on the data, detecting outliers and discovering existing correlated data. Then, the comparative method is used to explore the effectiveness of PCA dimensionality reduction method on the prediction accuracy by observing and analyzing tables and images. It is found that the PCA dimensionality reduction method plays a positive role for boosting the prediction accuracy, but the PCA method does not significantly improve the prediction accuracy for the data that has been processed and the dimension is not high.

Re-irradiation for recurrent cervical cancer: A single institutional experience

PurposeSalvage treatment of recurrent cervical cancer of patients with a history of radiotherapy is currently a major clinical challenge. The purpose of our study was to retrospectively analyze clinical outcomes of radiation in patients with recurrent cancer who have previously received radiotherapy at our hospital and further explore the efficacy and safety of this treatment modality. MethodsAll consecutive patients who underwent re-irradiation were included in our department between January 2015 and December 2017. All the patients received Volumetric Modulated Arc Therapy (VMAT) alone or VMAT followed by three dimensional–image-guided brachytherapy (3D-IGBT). The volume and dose for re-irradiation depended on previous radiation fields, dosimetry and recurrence sites. All patients received systemic chemotherapy before or after re-irradiation. ResultsFifty patients were included in our study. The median time from primary radiotherapy to re-irradiation was 12 months. Local recurrence, which was the most common failure following primary treatment, was present in 25 patients (50.0 %) while regional recurrence, loco-regional recurrence and distant recurrence combined in-filed recurrence was present in 8 (16.0 %), 9 (18.0 %) and 8 patients (16.0 %). Re-irradiation dose to lymph nodes was 45 Gy with or without a boost up to 55–60 Gy, and to the gross mass was 36–45 Gy with or without a boost up to 45–61 Gy. The median follow-up period was 22 (range,4–59) months. The 3-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 58.0, 38.7, and 44.4 %, respectively. The median time of PFS and OS was 14 and 26 months, respectively. The interval between two successive radiotherapies beyond 12 months was significantly associated with better LC and PFS (p ≤ 0.05), but without the benefit of OS (p > 0.05). Serum SCC antigen level less than 1.5 ng/ml had a significantly better impact on PFS (p ≤ 0.05). Overall, 14 patients (28 %) experienced ≥ grade 3 acute toxicities, while 9 (18 %) experienced ≥ grade 3 late toxicities. ConclusionsRe-irradiation with VMAT is an effective and safe salvage treatment option with a reasonably good clinical outcome and toxicity profile in selected patients. In our experience, recurrent cancer patients with an interval between two successive radiotherapy courses beyond 12 months and with a serum SCC-Ag level less than 1.5 ng/ml, had improved outcomes.

Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients.

The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study. All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB). The analysis included 106 cancer patients. Their median age was 60 years (IQR 50-69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156-484), the incidence of VTE recurrences was 3.8% (95%CI 1.0-9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1-10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6-8.1). Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

Effect of regional anesthesia and analgesia on long-term survival following abdominal cancer Surgery-A systematic review with meta-analysis

BackgroundThe impact of regional anesthesia and analgesia (RAA) on long-term survival following cancer surgery is a topic of debate. The aim of this study was to investigate the effects of perioperative RAA on long-term oncological outcomes in patients undergoing major abdominal cancer surgery. MethodsThe authors searched computerized databases and reference lists from inception to December 20, 2022. All studies that investigated the effects of perioperative RAA on long-term oncological outcomes following major abdominal cancer surgery were included. Using the inverse variance method with a random-effects model, hazard ratios (HR) and 95% confidence intervals (CI) were calculated. ResultsThe systematic review included 51 retrospective studies, one prospective study, and three randomized controlled trials (RCTs), with a total of 95,046 patients. The results showed that perioperative RAA may improve long-term overall survival (HR: 0.85, 95% CI: 0.80 to 0.91, P = 0.00, I2 = 60.2%). However, there was no significant association between perioperative RAA and reduced cancer recurrence (HR: 0.98, 95% CI: 0.90 to 1.03, P = 0.31, I2 = 52.3%). When performing a pooled analysis of the data from the three RCTs, no statistically significant effect of RAA was found in either case. ConclusionThe systematic review suggests perioperative RAA may improve long-term overall survival but does not appear to reduce cancer recurrence in patients undergoing major abdominal cancer surgery. The limited number of RCTs included in this study did not confirm this finding, highlighting the need for further RCTs to corroborate these results.

Clinical Usefulness of PSMA PET/CT Imaging in Patients with Suspected Recurrence of Prostate Cancer after Primary RT with PSA below the Phoenix Criteria Threshold: Systematic Review and Meta-Analysis

To assess the detection rate and the patterns of PSMA PET/CT uptake in patients with suspected prostate cancer recurrence after primary radiotherapy with serum PSA levels below the accepted Phoenix definition criteria for biochemical recurrence. The meta-analysis was performed according to the PRISMA statement. Studies providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with serum PSA levels below the accepted Phoenix definition criteria were included. Atotal of 5 studies included a total of 1334 patients, of which 489 patients with suspected BCR and serum PSA levels below the Phoenix criteria were included. The PSMA PET/CT detection rate (DR) was 60% for PSA <0.5 ng/mL, 76% for PSA 0.5-1 ng/mL, 81.03% for PSA 1-2 ng/mL, and 89.5% for PSA>2. No significant differences were found in the locations of PSMA-PET/CT uptake among those with PSA ≤2 ng/mL, compared with those meeting the Phoenix criteria. The PSMA-PET/CT uptake of local-only recurrence was more likely in patients with PSA <2 ng/mL (local-only recurrence PSA >2 ng/mL [40.07%] vs PSA <2 ng/mL [58.10%]), RR: 0.718 (95% CI: 0.579-0.892). Lymph node, bone, and visceral metastasis detection rates could be extracted from 3 studies (432 patients). For lymph nodes, the DR was 46% (95% CI: 38-54) in patients outside the Phoenix criteria threshold, and 50% (95% CI: 39-62) in patients with PSA>2 ng/mL. The DR for bone metastases was 19% (95% CI: 12-28) in patients outside the Phoenix criteria threshold, and 25% (95% CI: 19-31) in patients with PSA>2 ng/mL. The DR for visceral metastases was 3% (95% CI: 0-7) in patients outside the Phoenix criteria threshold, and 2% (95% CI: 0-4) in patients with PSA>2 ng/mL. The potentially salvageable disease was considered when all evidence of avid disease could be safely treated with local therapy. This data could be extracted from two studies (343 patients). A higher proportion of disease potentially amenable to salvage therapy was reported in patients outside the Phoenix criteria threshold [salvageable disease: PSA ≤2 ng/mL: 69% (95% CI: 57-80), and PSA >2 ng/mL: 61% (95% CI: 55-66). The pooled risk ratio meta-analysis showed no statistically significant differences between the two previous groups RR: 0.91 (95% CI: 0.75-1.10). PSMAPET/CT can detect prostate cancer recurrence in patients with PSA levels below the Phoenix criteria threshold (reaching up to 80%). Local-only recurrence detection by PSMA PET/CT was more likely in patients with PSA <2 ng/mL. The data from the present meta-analysis shows that a critical review of the Phoenix criteria in the era of PSMA PET/CT might be warranted. Nevertheless, the lack of anatomopathological validation and the retrospective nature of the studies are some of our limitations.

Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment.

The utilization of neoadjuvant therapy is progressively expanding in various clinical settings. However, the absence of a clinically validated biomarker to evaluate the treatment response remains a significant challenge in the field. Circulating tumor DNA (ctDNA) detection, a novel and emerging monitoring approach in the field of oncology, holds promise as a potential prognostic biomarker for patients with cancer. This meta-analysis investigated the clinical significance of ctDNA detection as a predictive tool for cancer recurrence in patients receiving neoadjuvant treatment. A comprehensive systematic literature search was conducted using public databases to identify relevant studies that investigated the association between ctDNA detection and cancer recurrence in patients receiving neoadjuvant treatment. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CI) were calculated to assess the relationship between cancer recurrence and relevant factors. Cancer recurrence was considered the primary outcome. A total of 23 studies encompassing 1590 patients across eight different cancer types were included in the final analysis. Positive ctDNA detection was significantly associated with higher cancer recurrence, especially at post-neoadjuvant treatment and post-surgery time points. The risk values for the different cancer categories and geographic areas also differed significantly. Our comprehensive meta-analysis revealed a significant positive correlation between ctDNA detection and a higher risk of cancer recurrence in patients receiving neoadjuvant treatment. In addition, the risk of recurrence was influenced by variations in cancer type, timing of detection, and geographic region. These findings highlight the promising clinical applicability of ctDNA as a prognostic marker and monitoring approach for patients with cancer. However, the precise mechanism is unknown and more evidence is needed for further research.

The accuracy of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of ovarian cancer relapse in patients with rising cancer antigen 125 (CA-125) levels

Background18F-fluorodeoxyglucose (FDG) PET/CT is a noninvasive imaging tool that has been used successfully for the diagnosis, staging, restaging, therapy monitoring, and prognostic prediction of ovarian cancer. For ovarian cancer surveillance, rising CA-125 levels raise the suspicion of recurrence despite its reported low specificity; being elevated in other benign and inflammatory conditions, and thus, confirmation is required. This work aimed to evaluate the role of 18F-FDG PET/CT in suspected ovarian cancer recurrence in patients presenting with elevated CA-125 levels.ResultsFifty female patients with suspected ovarian cancer recurrence owing to elevated CA-125 levels were included in this study. Recurrence was confirmed in 46/50 cases whether by histopathological confirmation or by serial follow-up imaging and clinical follow-up. Positive PET/CT findings were reported in 45/50 cases with 2 false-negative cases and 1 false-positive case. PET/CT examination was found to be superior to contrast-enhanced CT in the detection of peritoneal metastatic nodules and metastatic lymph nodes. According to this study, the estimated sensitivity, specificity, and overall diagnostic accuracy of PET/CT in the detection of recurrent ovarian cancer were 95.6%, 75%, and 94%, respectively.ConclusionsIn ovarian cancer surveillance, 18F-FDG PET/CT was found to be a sensitive and accurate noninvasive imaging tool that can be used in the detection of recurrent ovarian cancer in patients with elevated CA-125 levels, thus interfering with the management plan. The advantage of whole-body imaging in PET/CT allows for the detection and precise localization of recurrent or metastatic foci in abdominal and extra-abdominal sites as well.

Early on-treatment C-reactive protein and its kinetics predict survival and response in recurrent and/or metastatic head and neck cancer patients receiving first-line pembrolizumab.

First-line immune checkpoint blockade has improved the prognosis of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but response rates remain low. In this study, we aimed to investigate the prognostic value of CRP and its early kinetics to predict response and survival in R/M HNSCC. A total of 87 patients who received first-line pembrolizumab for R/M HNSCC were analyzed. Three-fold cross-validation was used to estimate cut-off points of CRP at baseline and on-treatment (day 40 ± 10). Treatment response and survival were analyzed according to early CRP kinetics. The neutrophil-to-lymphocyte ratio (NLR) was used as a benchmark for the prognostic performance of CRP. On-treatment CRP below 2mg/dl, 4x the upper limit of normal (ULN), was associated with increased overall survival (OS), while on-treatment CRP below 3mg/dl (6x ULN) was correlated with a higher disease control rate (DCR) and increased progression-free survival (PFS). CRP flare-responders and CRP responders showed a higher DCR and longer PFS than CRP non-responders. An NLR above 6 was a negative prognosticator for progression. In multivariable analysis, on-treatment CRP prevailed as the only significant prognosticator for OS (HR: 4.97, CI95%: 2.18-11.32, p < 0.001) and PFS (HR: 2.07, CI95%: 1.07-3.99, p = 0.030). On-treatment CRP was identified as a prognostic biomarker for objective response and survival in R/M HNSCC patients receiving first-line pembrolizumab and could be easily incorporated into clinical practice as a widely available and cost-effective biomarker.

Risk of Cancer Recurrence in Patients With Immune-Mediated Diseases With Use of Immunosuppressive Therapies: An Updated Systematic Review and Meta-Analysis

There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer biologic and small-molecule treatments. We performed a systematic search of PubMed and Embase databases to identify studies examining the impact of immunosuppressive therapies on cancer recurrence across several immune-mediated diseases. Studies were pooled together using random-effects meta-analysis and stratified by type of treatment. Primary outcome was occurrence of incident cancers, defined as new or recurrent. Our meta-analysis included 31 studies (17 inflammatory bowel disease, 14 rheumatoid arthritis, 2 psoriasis, and 1 ankylosing spondylitis) contributing 24,328 persons and 85,784 person-years (p-y) of follow-up evaluation. Rates of cancer recurrence were similar among individuals not on immunosuppression (IS) (1627 incident cancers, 43,765 p-y; 35 per 1000 p-y; 95% CI, 27-43), receiving an anti-tumor necrosis factor (571 incident cancers, 17,772 p-y; 32 per 1000 p-y; 95% CI, 25-38), immunomodulators (1104 incident cancers, 17,018 p-y; 46 per 1000 p-y; 95% CI, 31-61), combination immunosuppression (179 incident cancers, 2659 p-y; 56 per 1000 p-y; 95% CI, 31-81). Patients receiving ustekinumab (5 incident cancers, 213 p-y; 21 per 1000 p-y; 95% CI, 0-44) and vedolizumab (37 incident cancers, 1951 p-y; 16 per 1000 p-y; 95% CI, 5-26) had numerically lower rates of cancer. There were no studies on Janus kinase inhibitors. Stratification of studies by timing of immunosuppression initiation did not reveal a medication effect based on early (<5 years) or delayed treatment initiation. In patients with immune-mediated diseases and a history of malignancy, we observed similar rates of cancer recurrence in those on no immunosuppression compared with different immunosuppressive treatments.

Effectiveness of Internet-Based Cognitive Behavioral Therapy for Patients With Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Internet-based cognitive behavioral therapy (ICBT) is a relatively new therapy with unknown effectiveness in patients with cancer. In addition, therapist-guided and self-guided ICBT patient-specific outcomes for cancer patients remain to be explored. To explore the effects of ICBT on psychological outcomes, physical outcomes, and daily life outcomes in patients with cancer. Electronic databases such as PubMed, Web of Science, Cochrane Library, EMBASE, APA PsycINFO, ProQuest, and ClinicalTrials.gov were searched for relevant studies published from their inception to October 2022. Five GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) considerations were used to assess the quality of relevant evidence. Data analysis was performed via RevMan 5.4 (The Cochrane Collaboration, London, United Kingdom) and Stata 15.0 (StataCorp, College Station, Texas). Three thousand two hundred forty-nine participants from 20 studies were included in the meta-analysis. Statistically significant effects of ICBT were found on psychological distress, quality of life (QOL), anxiety, and depression, after the intervention. A separate analysis of follow-up data showed that ICBT had a sustainable effect on psychological distress, anxiety, and depression. Subgroup analyses showed that therapist-guided ICBT was more effective for psychological distress and QOL. Internet-based cognitive behavioral therapy can improve symptom management for patients with cancer. Internet-based cognitive behavioral therapy effectively improves psychological distress, anxiety, and depression in patients with cancer after intervention and at follow-up. Internet-based cognitive behavioral therapy improved QOL for cancer patients postintervention but not during follow-up. Internet-based cognitive behavioral therapy did not relieve fatigue or fear of recurrence in cancer patients. Therapist-guided ICBT is recommended for its superior outcomes in alleviating psychological distress and improving overall QOL in adults with cancer when compared with self-guided ICBT.

A novel, AI-generated morphologic biomarker to predict prostate cancer recurrence in patients with intermediate risk of progression.

e17097 Background: About half of the prostate cancer (PCa) patients within an intermediate-risk group return to the clinic with disease progression after the first line of therapy. While these patients can be stratified into Gleason Grades (GG) 3+4 and 4+3, studies indicate that high-risk patients can still be found in both groups. Using our AI platform, we have developed a morphometric biomarker by analyzing digitized H&amp;E slide images (WSIs), which can accurately predict early biochemical recurrence (within 36 months post-surgery) and the risk of metastatic disease more accurately than GG, TNM staging, and genomic tools. Methods: 125 intermediate-risk (n = 67, 3+4; n = 58, 4+3) samples were collected from the Icahn School of Medicine at Mount Sinai (ISSMS) to form a held-out test set. Seventy-eight patients within the test set had an associated genomic score. A series of deep learning models trained using data from ISMMS, the University of Wisconsin-Madison, and TCGA generated a high dimensional vector for each WSI to provide a numerical representation of observed morphologies, which is then converted into a single score to predict biochemical recurrence within 36 months (BCR) and rank risk of metastasis (MET). Area-under-the-receiver operating characteristic (AROC) was used to measure the accuracy of BCR, and the concordance index (CI) was used to measure the performance of MET. The high and low-risk groups' hazard ratios (HR) for patients within grades 3+4 and 4+3 show that our model can further stratify GG. Results: Our method was significantly better at predicting BCR (AROC: 0.801) and ranking MET (CI: 0.764) relative to GG, TNM, and genomic tool (Table 1). We further sub-stratified the patients into GG 3+4 and 4+3 and identified high-risk patients within each GG. Patients in GG 3+4 with high PATHOMIQ scores had a significantly higher risk of BCR (HR 3.3; 95% CI 1.44 – 7.56; p &lt; 0.005) compared to the low PATHOMIQ score patients. A similar trend was seen in the GG 4+3 group (HR 3.0; 95% CI 1.32 – 6.83; p &lt; 0.01). Conclusions: Our histopathology-based prognostic biomarker significantly improves over standard clinical markers in stratifying patients with intermediate-risk PCa for BCR and MET. Our method overcomes several limitations of genomic testing: We only need digitized WSIs. Our method is non-destructive and preserves the tissue for further interrogation. Moreover, our turn-around time is a few hours. Thus, the PATHOMIQ scoring method may strongly impact the management of intermediate-risk PCa patients and clinical trial patient selection for the successful development of new therapies for early-stage PCa. [Table: see text]

Venous Thrombosis Recurrence After Catheter-Related Upper Extremity Deep Venous Thrombosis in Cancer Patients: A Retrospective Analysis.

Long-term indwelling central venous catheters (CVC) are frequently used to secure vascular access to deliver injectable treatment. Catheter-related thrombosis (CRT) occurs in approximately 2-6% of cancer patients. We conducted a single-center retrospective study to assess the rate of venous thromboembolism (VTE) recurrence in cancer patients; 200 patients were included. Mean age was 56 ± 15.15years, median follow-up duration was 16.5 [range: 10-36] months. The incidence of recurrence was estimated using Gray's method for competing risk with death as the competing event of VTE. Recurrent VTE occurred in 25.5% of patients with a median occurrence time of 6.5 [range: 5-11.25] months. In case of recurrence, 94.6% of patients were treated for cancer and 80.4% of them received anticoagulants; 4 major bleeds and 17 non-major bleeds occurred during follow-up. In multivariate analysis, previous VTE (Hazard Ratio (HR) 2.48 (95% CI 1.42-4.32) and presence of CVC (HR 5.56 (95% CI 1.96-15.75) were significant recurrence risk factors. After a first episode of CRT, 25.5% of patients experienced VTE recurrence as UEDVT in 30 cases (55.5%), PE in 17 cases (31.5%), and DVT in 7 cases (13%), mostly during anticoagulation therapy. Anticoagulation therapy does not avoid CRT in case of cancer and must be balanced with hemorrhagic risk.

Risk factors for recurrent disease in small papillary thyroid cancers – a Swedish register-based study

AimsTo study the correlation between clinicopathological risk factors and the risk for intervention-requiring cancer recurrence in patients with small papillary thyroid cancers (sPTCs).Materials and methodsRecords for 397 patients with sPTC (T1 ≤ 20mm) were obtained from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) between 2010 and 2016. Follow-up time was at least 5 years. Data regarding intervention-requiring cancer recurrence were obtained from patient medical records and analysed regarding lymph node (LN) status (N0, N1a and N1b) and recurrence.ResultsAge was significantly lower in the N1a and N1b groups compared to N0 (45 vs. 40.5 vs. 49 years, respectively; p = 0.002). Tumour size was smaller in the N1a group compared to N1b group (9 vs. 11.8 mm; p <0.01). The mean number of metastatic LNs at initial surgery was higher in the N1b compared to N1a group (6.6 vs. 3; p = 0.001), and in the recurrent compared to the non-recurrent group (7 versus 3.9; p <0.01). The recurrence rate was higher in the N1b group than the N1a and N0 groups (25% vs. 2.4% vs. 1.4%, respectively; p = 0.001).ConclusionsLymph node stage N1b at diagnosis, and having five or more metastatic nodes, are strong risk factors for cancer recurrence and decreased disease-free survival in sPTC. The management of patients with sPTC should include thorough lymph node mapping for optimal treatment and individual risk stratification.

Telomere length in multiple cancer: Insight into recurrence risk from a Meta-analysis.

Several studies have revealed the relationships between telomere length and the risk and mortality of numerous cancers. This meta-analysis aims to insightfully clarify the potential relationship between telomere length and the recurrence of multiple cancers. PubMed database was used to search and identify interrelated citations. These reports investigated the relationship between telomere length and various cancer recurrences. Meta-analysis pooled data from studies that reported risk ratio (RR) of 95 (CI = 95%) confidence intervals and/or P-values. The cancer recurrence was investigated from an overall standpoint to the multiple levels of subtypes of cancers. The meta-analysis involved 5,907 recurrent multiple cancer patients from 13 cohort studies. Compared to these cancer recurrence cases and the telomere length differences, there was no significant correlation between telomere length and cancer recurrence risk (short telomeres versus long telomeres; RR = 0.93, 95% CI: 0.72~1.20, P = 0.59). Additionally, a negative association was observed between telomere length and cancer recurrence in gastrointestinal cancer and a positive association in head and neck cancer, while telomere length had little effect on the recurrence of hematological malignancies and genitourinary cancer in this analysis. There was no significant relationship between recurrence and telomere length in 5,907 cases in 13 studies. However, there was a correlation between specific tumors. These results suggested that telomere length as a recurrence marker or telomere length to determine the possibility of recurrence must be evaluated on the specific type of cancer.

Abstract 4463: Prognostic significance of systemic inflammatory markers in recurrent or metastatic head and neck cancer patients treated with nivolumab

Abstract Treatment strategies for head and neck cancer has been improved with the contribution of immunotherapy. In spite of the fact, the mechanisms underlying the response to immune checkpoint inhibitors (ICIs) remain unclear, and discovery of the biomarker predicting therapeutic efficacy of ICIs is urgently required. Our previous study indicated that in patients with recurrent or metastatic head and neck squamous cell carcinoma treated with nivolumab, circulating T cells showed dynamic alterations depending on treatment efficacy using flow cytometry and mass cytometry. However, these analyses are somewhat complicated to apply each patient in clinical setting. In this study, we focused on systemic inflammatory markers, including inflammatory makers such as blood cell fractions and C-reactive protein(CRP) in peripheral blood. Firstly, we assessed the pretreatment systemic inflammatory markers in 61 recurrent or metastatic head and neck cancer patients treated with nivolumab, and determined whether these markers were associated with treatment responses by Kaplan-Meier method, multivariate analysis, regression analysis and classification and regression trees(CART). Next, we investigated circulating T cell subsets in 36 recurrent or metastatic head and neck cancer patients using flow cytometry. High neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio(PLR), and systemic immune-inflammation index(SII) significantly associated with poor prognosis in overall survival (NLR: p=0.0047, PLR: p=0.0357, SII: p=0.0011). Furthermore, high albumin, lymphocyte to monocyte ratio(LMR), and prognostic nutritional index(PNI) were significant good prognostic markers of overall survival (albumin: p=0.0037, LMR: p=0.0088, PNI: p=0.037). Overall survival time were estimated the values that were defined systemic inflammatory markers by multivariate analysis. These systemic inflammatory markers were assigned importance by each coefficient. Notably, the number of monocyte and lymphocyte have a strong influence on overall survival time. In addition, the index that were depending on the number of white blood cells and monocyte, the percentage of lymphocyte, platelet count, albumin, and PNI were useful prognostic tools in analyzing regression analysis. Furthermore, the evaluation of PNI were contributed to the predict treatment efficacy in analyzing CART. Moreover, NLR, PLR, and SII were positively correlated with the proportion of Treg (NLR: R2=0.3622/p=0.0001, PLR: R2=0.4198/p&amp;lt;0.0001, SII: R2=0.3654/p&amp;lt;0.0001). We concluded that in recurrent or metastatic head and neck cancer patients treated with nivolumab, systemic inflammatory markers could provide new insight into rational therapeutic strategies in cancer immunotherapy for head and neck cancer. Citation Format: Hiroe Tada, Kazuaki Chikamatsu. Prognostic significance of systemic inflammatory markers in recurrent or metastatic head and neck cancer patients treated with nivolumab. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4463.

Abstract 62: Untangling the connection between stress and metastatic breast cancer

Abstract There is emerging evidence that exposure to chronic stress is associated with increased risk of metastasis and poor survival in cancer patients. However, the underlying molecular and cellular mechanisms responsible for the effects of stress on tumor progression remain unclear. To determine how stress promotes metastasis, we established new mouse models in which multiple chronic stress exposure promoted breast cancer metastasis to the lungs. We found that chronic stress generates a pro-metastatic lung microenvironment with e.g., reduced T cell infiltration and increased extracellular matrix (ECM) deposition and neutrophil infiltration. Among them, neutrophils were required for these changes as their depletion abolished the pro-metastatic effects of stress and normalized the lung tumor microenvironment. Mechanistically, we analyzed neutrophils from chronically stressed mice and identified dramatically altered transcriptomes, including increased expression of several glucocorticoid receptor regulated genes. Phenotypically, neutrophils from stress exposed mice exhibited increased ROS production, and an increased ability to inhibit T cell activation and to form spontaneous neutrophil extracellular traps (NETs). The stress-associated changes to neutrophils were dependent on glucocorticoid receptor (GR) signaling as neutrophil-specific GR knockout mice showed no increase in NET-formation, a normalized lung microenvironment and no increase in lung metastasis upon stress exposure. Among the changes in the neutrophils caused by stress exposure, we found that the formation of pro-metastatic NETs was critical as directly digesting NETs with DNase I prevented stress-induced metastasis and normalized the lung microenvironment. In sum, this work shows that chronic stress exposure causes a glucocorticoid-mediated increase in NET formation and that NETs are critical drivers in the establishment of a stress-induced, metastasis-promoting microenvironment. Targeting NETs could be an important strategy to prevent metastatic recurrence in cancer patients, many of whom will experience stress due to their cancer diagnosis and subsequent treatments. Citation Format: Xue-Yan He, David Ng, Yuan Gao, Evdokia Michalopoulou, Shanu George, Jose M. Adrover, Lijuan Sun, Jean Albrengues, Ledong Wan, Xiao Han, Christopher Vakoc, Linda Van Aelst, Mikala Egeblad. Untangling the connection between stress and metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 62.

Abstract 4381: Predictive risk factors for cancer thrombosis in gastric cancer patients

Abstract Background Gastric cancer is strongly associated cancer thromboembolism. We aimed to identify the Khorana risk score (KRS) and other risk factors for cancer thromboembolism in patients with gastric cancer after gastrectomy. Methods We reviewed 610 gastric patients, who had undergone D2 radical gastrectomy between January 2005 and December 2017. Kaplan-Meier survival analysis and Cox regression models were used to evaluate for independent predictor of cumulative incidence of cancer thromboembolism and survival. Results The median follow up was 67.0 months. There were 35 (5.7%) caner thromboembolism. The cumulative incidences of thromboembolism were 6.1%, 3.1%, 3.3%, and 20.7% in stages I, II, III, IV. 181 (29.7%) patients were relapsed cancer and 159 (26.1%) patients were died. A high KRS (cumulative incidence 5.8%) was not associated with cancer thromboembolism compared to an intermediate KRS (cumulative 5.7%) (HR=1.005, 95% CI = 0.540-2.061, P= 0.876). After gastrectomy, recurrent cancer (cumulative incidence 9.9%) was associated with cancer thromboembolism compared to no recurrence (cumulative incidence 4.0%) (HR 3.713, 95% CI 1.879-7.335, P &amp;lt; 0.001). Conclusions Recurrent gastric cancer patients after gastrectomy were significantly increased cancer thromboembolism risk compared to no recurrent cancer patients. Among patients with gastric cancer after gastrectomy, KRS did not stratify the patients at high risk of cancer thromboembolism. Citation Format: Song Ee Park, Moon Ki Jung, In Gyu Hwang. Predictive risk factors for cancer thrombosis in gastric cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4381.

The added values of 18F-FDG PET/CT in differentiating cancer recurrence and osteoradionecrosis of mandible in patients with treated oral squamous cell carcinoma

BackgroundOsteoradionecrosis (ORN) of the jaw requires a differential diagnosis to exclude cancer recurrence. Here, we sought to develop a scoring system comprising 18F-FDG PET/CT parameters for distinguishing between the two conditions in patients with oral squamous cell carcinoma (OSCC).MethodsThe study consisted of 103 OSCC patients with suspected ORN of the jaw. All participants underwent 18F-FDG PET/CT imaging within 6 months of diagnostic histopathology. Following extraction of PET parameters, we identified clinical and imaging predictors of mandibular recurrence-free survival (MRFS) using receiver operating characteristic curve analysis and multivariate Cox regression models.ResultsThe results of histopathology revealed mandibular cancer recurrence in 24 patients (23.3%). Multivariate Cox regression analyses identified an age at diagnosis ≤ 52 years (P = 0.013), a location of the SUVmax voxel with soft tissue predominance (P = 0.019), and mandibular total lesion glycolysis (TLG) > 62.68 g (P < 0.001) as independent risk factors for MRFS. A scoring system was devised with scores from 0 (no risk factor) to 3 (presence of all three risk factors). High-risk patients with a score of 2–3 compared with score of 0–1 had a significantly higher likelihood of mandibular cancer recurrence (hazard ratio: 32.50, 95% confidence interval: 8.51–124.18, P < 0.001). The scoring system had a sensitivity of 87.50%, a specificity of 82.28%, and an accuracy of 83.50% for identifying mandibular cancer recurrence.ConclusionsThe scoring system of our study is clinically useful for identifying mandibular cancer recurrence in patients with suspected ORN of the jaw.

The role of long non-coding RNA UCA1 and MALAT1 in bladder cancer patients

BackgroundBladder cancer (BC) is considered the most prevalent tumor of the urinary tract, and incidence rates are rising globally. Long noncoding RNAs (lncRNAs) can serve as biomarkers to help the diagnosis and anticipation of recurrence in cancer patients as they are implicated in carcinogenesis and tumor progression. This study targeted to investigate the expression of lncRNA as urothelial cancer associated 1 (UCA1) as well as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the diagnosis of BC. Subjects and methodsThe study included 70 BC patients, 70 benign urinary tract diseases and 70 controls. The UCA1 and MALAT1 expressions were studied utilizing quantitative real-time polymerase chain reaction. ResultsThe UCA1 and MALAT1 expression were significantly increased in patients with BC than patients with chronic cystitis and controls (p < 0.001). The sensitivity and specificity for the diagnosis of BC for UCA1(87.14%, 97.14% respectively) and MALAT1 (92.86%, 90% respectively). Multivariate logistic regression analysis showed that UCA1 and MALAT1 were risk factors for the development of BC where the odds ratio (OR) for UCA1 was 1.262 (CI 1.004–1.587) and MALAT1 was 2.201(CI 1.036–4.676). ConclusionUCA1 and MALAT1 could be potential diagnostic biomarkers with good specificity and sensitivity in bladder cancer.

Association between physical activity and the time course of cancer recurrence in stage III colon cancer

ObjectiveWe determined if postoperative physical activity prevents or delays cancer recurrence in patients with stage III colon cancer.MethodsThis cohort study nested within a randomised trial enrolled 1696 patients with surgically...