Overall Survival In Early-stage Patients Research Articles

Construction and validation of prognostic nomogram and clinical characteristics for ovarian endometrioid carcinoma: an SEER-based cohort study

BackgroundOvarian endometrioid carcinoma (OEC) is the second most commonly occurring ovarian epithelial malignancy, but the associated prognostic factors remain obscure. This study aimed to analyze independent prognostic factors for patients with OEC and to develop and validate a nomogram to predict the overall survival (OS) of these patients.MethodsClinical information of patients with OEC (2000–2019) was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox analyses were used to identify independent prognostic factors, and nomogram models were constructed using independent prognostic factors. Receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA) were used to verify the accuracy and validity of the nomogram. Kaplan–Meier curves were used to compare the differences in OS and cancer-specific survival (CSS) among subgroups.ResultsA total of 4628 patients with OEC were included, being divided into training (n = 3238) and validation (n = 1390) sets (7:3 ratio). On multivariate Cox analysis, AJCC stage, age, tumor size, differentiation, chemotherapy, and lymph node resection were significant predictors of survival outcomes (P < 0.05). Resection of 1–3 lymph nodes in early-stage OEC patients did not significantly prolong OS (P > 0.05), but resection of ≥ 4 lymph nodes in early-stage improved OS and CSS (P < 0.05). The OS of early-stage patients was not related to whether or not they received chemotherapy (P > 0.05). Lymph node resection and chemotherapy significantly improved the prognosis of patients with advanced OEC (P < 0.05). The c-index of nomogram prediction model was 0.782. ROC with good discrimination, calibration plots with high consistency, and DCA with large net benefit rate result in large clinical value.ConclusionAJCC stage, differentiation, tumor size, age, chemotherapy, and lymph node dissection were prognostic factors of OEC. The constructed nomogram prediction model can effectively predict the prognosis of OEC patients and improve the accuracy of clinical decision-making.

Commercial next generation sequencing in a real-world cohort of patients with metastatic breast cancer.

e13082 Background: Clinicians increasingly order next generation sequencing (NGS) of tissue or liquid (ctDNA) biopsies from patients with metastatic breast cancer. Although some genetic information is clinically actionable, some, particularly non-ERBB2 gene amplifications, is not. We reviewed NGS data from a real-world cohort of metastatic breast cancer patients to evaluate the prevalence of somatic abnormalities using commercial NGS technology. Methods: We evaluated Foundation One NGS data from 44 tissue and 17 liquid biopsies from patients seen in a medical oncology practice between 2016 and 2022. We used KM Plotter to measure overall survival in early-stage patients by relative gene expression. Results: 76% of patients had ductal and 24% had lobular carcinomas. 59% of patients had luminal (ER-positive) and 32% of patients had basal breast cancer (ER-negative). Only 9% of patients had HER2-positive disease. 48% of the tumors had a p53 abnormality, either a point (59%) or frameshift mutation (36%). 50% tumors had a somatic mutation in a tumor suppressor gene such as PTEN, RB or APC. One patient had a germline BRCA1 mutation and 5 patients had germline BRCA2 mutations. 39% of patients carried a somatic mutation in PIK3CA, predominantly H1047R (45%) in the kinase domain or E545X (20%) in the helicase domain. KM plotter showed worse OS in early-stage patients with low p53 gene expression or high PIK3CA expression. 10/11 patients with lobular carcinoma had somatic mutations in CDH1, 70% of which were frameshift mutations. 8/27 patients with luminal cancer had an ESR1 mutation, predominantly Y537 or D538. 9 patients, predominantly luminal, had amplifications of the 11q13 (CCND1). 7 patients had amplifications of 8q24 (MYC). 20q13 (AURKA) amplifications were only seen in luminal cancers. 12p13 (CCND2) amplifications were only seen in basal cancers. 27% of lobular cancers (vs. 6-17% of ductal cancers) demonstrated amplification of the 11q13, 8q24 and/or 8p11 amplicons. 20q13 and 12p13 amplifications were only seen in ductal cancers. Liquid biopsies were more likely to detect point mutations than tissue biopsies. p53 mutations were seen in 65% of liquid vs. 48% of tissue biopsies. 47% of liquid biopsies showed two p53 mutations. PIK3CA mutations were seen in 71% of liquid vs. 39% of tissue biopsies. 18% of liquid biopsies showed two PIK3CA mutations. 93% of basal cancers had at least one p53 mutation. 44% of luminal cancers had a PIK3CA mutation. ESR1, GATA3 and AKT1 mutations were only seen in luminal cancers. While ESR1 mutations were seen in ductal and lobular cancers, GATA3 and AKT1 mutations were only seen in ductal cancers. Conclusions: Commercial NGS testing of a real-world cohort yields actionable mutations that can impact clinical management and outcome of metastatic breast cancer patients. NGS testing demonstrates the range of gene amplifications and corresponds closely with what has been reported in the published literature.

Role of radiation therapy in primary tonsil large B cell lymphoma: a SEER-based analysis

BackgroudPrimary tonsil diffuse large B cell lymphoma (PT-DLBCL) is an uncommon disease entity. The role of radiation therapy (RT) in PT-DLBCL is debatable in both the pre- and post- rituximab era. The purpose of this study was to evaluate the treatment outcome and establish a prognostic model in PT-DLBCL based on the Surveillance, Epidemiology, and End Results (SEER) database.Materials and methodsData of 1214 PT-DLBCL patients diagnosed between 1975 and 2016 were extracted from SEER 18. The effect of RT was assessed for the entire cohort and subgroups by stages using univariate, multivariate Cox regression analyses and propensity score matching (PSM).ResultsThe entire cohort included 1043 patients with early-stage (ES) PT-DLBCL and 171 patients with advanced-stage (AS) disease. A decreasing trend of RT utilization in the ES cohort after 2002 was observed. 47.4% of patients in ES received RT, whereas 25.1% in AS underwent RT. RT significantly improved overall survival in both univariate (P < 0.001) and multivariate (P = 0.002) analyses. PSM analysis further validated the survival advantage of RT (P = 0.002). A nomogram was established to predict the potential survival benefit. Subgroup analysis revealed RT was significantly associated with overall survival in ES patients of PT-DLBCL (P = 0.001) and in the rituximab era (P = 0.001) but not in those with AS disease (P = 0.241).ConclusionsThis population-based study encloses the largest sample of PT-DLBCL to date and demonstrates a favorable survival role of RT in early stages rather than advanced stages. The established nomogram helps to identify high risk patients to improve prognosis.

Assessment of the Circulating Tumor Cells and Microsatellite Instability in Colorectal Cancer Patients: Prognostic and Diagnostic Value.

BackgroundMicrosatellite instability (MSI) and circulating tumor cells (CTCs) play important roles in the diagnosis, prognosis and management of colorectal cancer (CRC) patients.MethodsCTCs and MSI were assessed in the blood and representative tumor tissues of 100 CRC patients by flow cytometry (FCM) and PCR amplification. The data were correlated to relevant clinicopathological features of the patients, progression-free survival (PFS) and overall survival (OS) rates.ResultsMSI-high was detected in 44 (44.0%) patients, MSI-low in 37 (37%), and microsatellite stable (MSS) in 19 (19.0%) patients (P=0.007). The baseline CTCs count (<4 cells/7mL blood) was reported in 39% of the patients, and CTCs ≥4 cells/7mL blood in 61% of the patients (P=0.028). Improved PFS and OS rates were associated significantly with MSI-high (P<0.001), decreased CTC levels during the course of treatment (P<0.001) and post-treatment CTCs (P=0.008). There was no significant association between MSI-high and PFS or OS in early-stage patients (P=0.187 and P=0.187; respectively); however, it was associated significantly with better PFS and OS in late-stage patients (P<0.001). Multivariate analysis showed that only a change in serial CTC levels is considered an independent prognostic factor for OS (P<0.012). Post-treatment CTCs level, serial CTCs level changes during the course of treatment, lymph nodes and distant metastasis were independent prognostic factors for PFS (P<0.001, P= 0.047, P=0.001 and P<0.001; respectively).ConclusionMSI and CTCs could be used as accurate, reliable and sensitive diagnostic and prognostic biomarkers for CRC patients’ survival rates and outcomes.

Nomograms for predicting survival in early-onset esophageal cancer

ABSTRACT Background: This study aimed to develop nomograms predicting the overall survival (OS) of patients younger than 50 years old with esophageal cancer. Methods: We selected patients included 2004–2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed using significant variables from multivariable Cox analyses. The discrimination and calibration power of the models were evaluated using concordance indexes (C-indexes) and calibration curves. Decision curve analysis was used to assess the clinical net benefits of the nomograms. Results: Of 1,997 selected patients, 53.2% had advanced-stage tumor. Race, grade, T stage, N stage, and treatment were independent factors affecting OS in early-stage patients. The C-indexes of the corresponding nomogram were 0.710 (95% CI = 0.684–0.736) and 0.681 (95% CI = 0.640–0.722) in training and validation sets, respectively. Grade, marital status, and treatment were independent factors affecting OS in advanced-stage patients. The C-indexes of the corresponding nomogram were 0.677 (95% CI = 0.653–0.701) and 0.675 (95% CI = 0.638–0.712) in training and validation sets, respectively. Calibration curves demonstrated high consistency between predicted and actual survival. Conclusion: We constructed and verified nomograms that could accurately predict the survival rate of esophageal cancer in patients younger than 50 years old. This may help clinicians better understand prognostic factors.

Clear Cell Adenocarcinoma of Uterine Cervix: A Single Institution Retrospective Experience.

PurposeThe purpose of the study is to summarize the clinical characteristics and identify the prognosis of clear cell adenocarcinoma of the uterine cervix (CCAUC) in patients without a history of diethylstilbestrol (DES) exposure.MethodsForty-two patients with CCAUC, treated initially at Sun Yat-sen University Cancer Center between 1985 and 2017, were studied.ResultsOf all the CCAUC patients, the median age was 47 years old, and the median tumor size was 3 cm. Thirty-four early stage patients (IB = 28, IIA = 6) underwent radical surgery. Eight advanced stage patients (IIB = 8) received concurrent chemoradiotherapy (n = 4) or radical surgery (n = 4). Survival analysis showed that patients with early stage (IB-IIA) had a significantly better 5–year progression-free survival (PFS) and overall survival (OS) than those with advanced stage (IIB) (p < 0.05). The patients with negative pelvic lymph node (PLN) had a significantly better 5-year PFS and OS than those with positive PLN (p < 0.05). Radiotherapy (RT) did not affect PFS or OS in early stage patients with intermediate risk factors (p > 0.05). Adjuvant chemotherapy (CT) did not affect PFS or OS in early stage patients without risk factors (p > 0.05).ConclusionThe FIGO stage and pelvic node status were important prognostic factors for both PFS and OS. For treatment modality, we recommended that radical surgery alone was used in early stage patients without high risk factors. Ovarian preservation in early stage patients involved some risk.

Abstract B20: Hypopharyngeal carcinoma management: 25-year experience from a tertiary care medical center in United States

Abstract Introduction: The purpose of this study is to evaluate the incidence, management, and prognosis of hypopharyngeal carcinoma in a tertiary care institution over the past 25 years. Methods: We retrospectively analyzed patients from 1995 to 2019 from the head and neck cancer data base of our institution. The data regarding the demographics, stage, treatment, and follow-up were collected. Outcomes including median survival and overall survival were evaluated using the Kaplan Meier method. All analyses were performed using SPSS version 24. Results: We identified 144 hypopharyngeal carcinoma patients, and the incidence was almost 4% of all head and neck cancers. All patients had squamous cell carcinoma. Sixty-one percent of patients were African Americans and 36% were Caucasians. Ninety percent of the patients were males, and 10% were females. Pyriform sinus was the subsite most commonly affected (67%), followed by posterior pharyngeal wall (10%) and postcricoid area (5%). Ninety-six percent of patients presented with advanced-stage disease (stages III and IV), with only 4% of patients presenting with early-stage disease (Stages I and II). Fifty-one percent of patients underwent definitive chemoradiotherapy with or without induction chemotherapy and 23% of patients underwent surgical management, followed by adjuvant radiation or chemoradiation, depending on risk factors. Ten percent of patients received only palliative chemotherapy and 15% did not receive any treatments. Induction chemotherapy was used in 31% of patients prior to initiation of definitive chemoradiation treatment. The median overall survival of early-stage patients and of advanced-stage patients was 56 months and 15 months, respectively. The median survival of the patients with advanced-stage patients who received definitive treatment was 26 months. The patients who underwent definitive operative management followed by adjuvant treatments had an improved median survival as compared to those undergoing definitive chemoradiation treatment (38 months vs. 16 months, p=0.05). Similarly, the overall survival at 3 years (30% vs. 54%, p=0.05) and 5 years (13% vs. 34%, p=0.05) was also better for surgery patients. The patients who received induction chemotherapy had clinically worse median survival as compared to those who did not, but this was not statistically significant (14 months vs. 21 months, p=0.2). Conclusions: Our results agree with the published literature regarding the low incidence of hypopharyngeal cancer, presentation in advanced stages, and poor long-term outcomes. Selection of patients for laryngeal preservation should be done very carefully. Our results suggest that trimodality treatment may be more efficacious than definitive chemoradiotherapy for locally advanced disease. Future studies are warranted to evaluate if neoadjuvant chemoradiotherapy followed by surgery might be able to improve the current poor outcomes for advanced hypopharyngeal cancer patients who are not eligible for laryngeal preservation. Citation Format: Toms Vengaloor Thomas, Mary R. Nittala, Divyang Mehta, Madhava Rao Kanakamedala, Anu Abraham, Lacey Weatherall, Eldrin Bhanat, Ashley A. Albert, Srinivasan Vijayakumar. Hypopharyngeal carcinoma management: 25-year experience from a tertiary care medical center in United States [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B20.

Decreased cytokeratin 7 expression correlates with the progression of cervical squamous cell carcinoma and poor patient outcomes

To identify potential biomarkers for tumor progression and patient outcomes in cervical squamous cell carcinoma. We examined the expressions of CK7 and CK17 as potential markers of the squamo-columnar junction, and podoplanin as a basal cell marker using surgical and biopsy samples of patients in grade 3 cervical intraepithelial neoplasia (n = 30), operable invasive carcinoma (OP group, n = 53) and inoperable invasive carcinoma before radiotherapy and/or chemotherapy (RC group, n = 76). The positive rates of CK7 and podoplanin in invasive carcinoma were significantly lower than those in grade 3 cervical intraepithelial neoplasia (P = 0.001, P < 0.0001). The positive rates of CK7 and podoplanin in the RC group were significantly lower than those in the OP group (P < 0.0001, P = 0.04), while CK17 expression showed significantly higher positivity in the RC group than in the OP group (P < 0.0001). Negative CK7 expression showed a potential impact on overall survival in early-stage patients. In the RC group, the prevalence of cases with post-therapeutic residual carcinoma cells was higher in the CK7-negative group than in the positive group (P = 0.003). We found that decreased expression of CK7 could be a prognostic factor in early-stage cervical cancer patients. This result may provide strategies and suggestions for new treatment options and follow-up practices in managing patients with cervical cancer.

SOX30 is a prognostic biomarker and chemotherapeutic indicator for advanced-stage ovarian cancer.

New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31-5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer. SOX30 coincidentally located at this chromosomal region has been determined as a new important tumor suppressor. However, the prognostic value, role and mechanism of SOX30 in ovarian cancer are unexplored. Here, we reveal that SOX30 is frequently overexpressed in ovarian cancer tissues and is associated with clinical stage and metastasis of ovarian cancer patients. High SOX30 expression predicts better OS and acts as an independent prognostic factor in advanced-stage patients, but is not associated with OS in early-stage patients. Based on the survival analyses, the advanced-stage patients with high SOX30 expression can receive platin- and/or taxol-based chemotherapy, whereas they should not receive chemotherapy containing gemcitabine or topotecan. Functionally, SOX30 strongly inhibits tumor cell migration and invasion in intro and suppresses tumor metastasis in vivo. SOX30 regulates some markers (E-CADHERIN, FIBRONECTIN, N-CADHERIN and VIMENTIN) and prevents the characteristics of epithelial-mesenchymal transition (EMT). SOX30 transcriptionally regulates the expression of E-CADHERIN, FIBRONECTIN and N-CADHERIN by binding to their promoters. Restoration of E-CADHERIN and/or N-CADHERIN when overexpressing SOX30 significantly reduces the anti-metastatic role of SOX30. Indeed, chemotherapy treatment containing platin or gemcitabine combined with SOX30 expression influences tumor cell metastasis and the survival of nude mice differently, which is closely associated with EMT. In conclusion, SOX30 antagonizes tumor metastasis by preventing EMT process that can be used to predict survival and incorporated into chemotherapeutics of advanced-stage ovarian cancer patients.

Role of Systematic Lymphadenectomy and Adjuvant Radiation in Early-Stage Endometrioid Uterine Cancer

To determine the roles of lymphadenectomy in endometrioid uterine cancer patients and adjuvant radiation in early-stage endometrioid uterine cancer patients who underwent systematic lymphadenectomy. A retrospective analysis of 758 patients surgically treated for early-stage endometrioid uterine cancer from 2000 to 2006 was conducted. The primary outcome was 5-year overall survival in relation to systematic lymphadenectomy with or without adjuvant radiation. Of the 758 patients, 547 (72.2%) underwent complete surgical staging, including systematic lymphadenectomy; adjuvant radiation was administered to 207 patients (27.3%). Within median follow-up of 35months, systematic lymphadenectomy did not affect overall survival in early-stage patients (P=0.4480). In the high-risk, early-stage group, however, the 5-year survival rate of the systematic lymphadenectomy group showed better survival compared with the no systematic lymphadenectomy group (P=0.0095). Also, adjuvant radiation did not affect overall survival in early-stage patients (P=0.1170), even in the group of high-risk, early-stage patients (P=0.5680) who underwent systematic lymphadenectomy. Systematic lymphadenectomy provided a survival benefit in high-risk endometrioid uterine cancer patients. However, in patients who underwent systematic lymphadenectomy, adjuvant radiation was not beneficial, even in high-risk patients.