Factor For Disease-free Survival Research Articles

BRCAness as a prognostic indicator in patients with early breast cancer

BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients. Forty-eight patients (39.7%) were identified as BRCAness positive. Tumors of BRCAness were more likely to be hormone receptors negative (95.8% vs. 50.7%, P < 0.001), nuclear grade III (76.1% vs. 48.4%, P = 0.001) and triple-negative breast cancer subtype (91.6% vs. 42.5%, P < 0.001). Five-year disease free survival (DFS) (54.0% vs. 88.0%, P < 0.001) and overall survival (OS) (76.3% vs. 93.1%, P = 0.002) were significantly lower in BRCAness patients. In neoadjuvant chemotherapy subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, P = 0.041). Cox regression multivariate analysis showed that BRCAness was the independent prognostic factor for DFS (HR 2.962, 95%CI 1.184–7.412, P = 0.020), but not for OS (HR 2.681, 95%CI 0.618–11.630, P = 0.188). BRCAness is associated with specific characteristics and may suggest resistance to taxane-based chemotherapy. BRCAness can be used as a negative prognostic indicator for breast cancer.

Laboratory parameters as predictors of prognosis in uterine cervical neoplasia

ObjectivesThe aims of study were to assess platelet counts, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), RWD (red cells distribution width) and fasting glucose in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer; and to relate these parameters to prognostic factors and survival in cervical cancer. Study DesignWe evaluated the patients with confirmed diagnosis of invasive cervical cancer (n = 102), and CIN (n = 102). Histological type, NLR, PLR, RDW, platelets count, fasting glucose, staging, overall survival (OS), and disease-free survival (DFS) were evaluated. The results of laboratory parameters were assessed by Mann-Whitney test. A receiver operating characteristic (ROC) curve was used to determine the best cut-off values. Survival was verified by the Kaplan-Meyer method followed by the Gehan-Breslow test. Multivariate analysis was performed using Cox regression. The level of significance was less than 0.05. ResultsComparing CIN and invasive malignancies, higher values of NLR, PLR, RDW and fasting glucose were found in cancer patients (p < 0.0001, p = 0.011, p = 0.0153 and p = 0.0096, respectively). In cervical cancer, higher NLR and PLR values were found at stage II to IV when compared to stage I (p = 0.0066 and p = 0.005, respectively). ROC curves were performed. In invasive neoplasms, the cut-off values for NLR and PLR in the comparison between stage I and greater than I were 4 and 165.45, respectively. For survival curves, there was lower OS and DFS in patients with NLR greater than 4 (p = 0.0004 and p = 0.0153, respectively) and PLR greater than 165.45 (p = 0.0319 and p = 0.0362, respectively). After multivariate analysis, only NLR remained as an independent factor in DFS (HR = 6.095, 95 % CI = 1.120–33.177, p = 0.037) and OS (HR = 4.522, 95 % CI = 1.241–16.479, p = 0.022) ConclusionHigher NLR is associated to lower OS and DFS in invasive uterine cervical neoplasia, and can be considered an independent factor of worse prognosis.

Liver resection for colorectal liver-limited metastases in elderly patients: a propensity score matching analysis

BackgroundFew studies have focused on the role of hepatectomy for colorectal liver-limited metastases in elderly patients compared to matched younger patients.MethodsFrom January 2000 to December 2018, 724 patients underwent hepatectomy for colorectal liver-limited metastases. Based on a 1:2 propensity score matching (PSM) model, 64 elderly patients (≥ 70 years of age) were matched to 128 younger patients (< 70 years of age) to obtain two balanced groups with regard to demographic, therapeutic, and prognostic factors.ResultsThere were 73 elderly and 651 younger patients in the unmatched cohort. Compared with the younger group (YG), the elderly group (EG) had significantly higher proportion of American Society of Anesthesiologists score III and comorbidities and lower proportion of more than 3 liver metastases and postoperative chemotherapy (p < 0.05). After PSM for these factors, rat sarcoma virus proto-oncogene/B-Raf proto-oncogene (RAS/BRAF) mutation status and primary tumor sidedness, the EG had significantly less median intraoperative blood loss than the YG (175 ml vs. 200 ml, p = 0.046), a shorter median postoperative hospital stay (8 days vs. 11 days, p = 0.020), and a higher readmission rate (4.7% vs.0%, p = 0.036). The EG also had longer disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS) compared to the YG, but these findings were not statistically significant (p > 0.05). Old age was not an independent factor for DFS, OS, and CSS by Cox multivariate regression analysis (p > 0.05).ConclusionsHepatectomy is safe for colorectal liver-limited metastases in elderly patients, and these patients may subsequently benefit from prolonged DFS, OS, and CSS.

The prognostic significance of inflammation-based scores in patients with ampullary carcinoma after pancreaticoduodenectomy

BackgroundGrowing evidence indicates that the systemic inflammatory response plays an important role in cancer development and progression. Several inflammatory markers have been reported to be associated with clinical outcomes in patients with various types of cancer. This study was designed to evaluate the prognostic value of inflammatory indexes in patients with ampullary cancer (AC) who underwent pancreaticoduodenectomy (PD).MethodsWe retrospectively reviewed the data of 358 patients with AC who underwent PD between 2009 and 2018. R software was used to compare the area under the time-dependent receiver operating characteristic (ROC) curves (AUROCs) of the inflammation-based indexes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI) and prognostic index (PI), in terms of their predictive value for survival. The survival differences of these indexes were compared by the Kaplan-Meier method and univariate and multivariate analyses were performed to determine the prognostic factors of disease-free survival (DFS) and overall survival (OS).ResultsThe estimated 1-, 2-, and 3-year OS and DFS rates were 83.9, 65.8, and 55.2% and 58.0, 42.8, and 37.8%, respectively, for the entire cohort. The survival differences were significant in terms of OS and DFS when patients were stratified by these inflammation-based indexes. The comparisons of the AUROCs of these inflammation-based indexes illustrated that NLR and PI displayed the highest prognostic value, compared to the other indexes. When NLR and PI were combined, NLR-PI showed even higher AUROC values and was identified as a significant prognostic factor for OS and DFS.ConclusionSpecific inflammatory indexes, such as NLR, PLR and dNLR, were found to be able to predict the OS or DFS of patients. As a novel inflammatory index, the level of NLR-PI, which can be regarded as a more useful prognostic index, exhibited strong predictive power for predicting the prognosis of patients with AC after the PD procedure.

Significance of accurate hilar and intrapulmonary lymph node examination and prognostication in stage IA\u2013IIA non-small cell lung cancer, a retrospective cohort study

BackgroundThe examination of lymph nodes (LNs) plays an important role in the nodal staging of non-small cell lung cancer (NSCLC). For patients without LN metastasis, the main role of thorough LN examination is accurate staging, which weakens the effect of staging migration. To date, the role of hilar and intrapulmonary (N1) station LNs has not been fully appreciated. In this study, we aimed to confirm the significance of N1 LNs in long-term survival for stage IA–IIA NSCLC patients and to find the minimum number of LN to examine.MethodsThe data of patients who underwent radical lobectomy and were confirmed as having non-metastatic LNs from January 2008 to March 2018 were retrospectively screened. Pathology records were reviewed for the number of LNs examined. The Kaplan-Meier method and Cox regression model were used to identify survival and prognostic factors.ResultsThe median number of resected N1 LNs was 8. The number of patients with 0–2 N1 LNs, 3–5 N1 LNs, 6–8 N1 LNs, 9–11 N1 LNs, and more than 11 N1 LNs examined was 181, 425, 477, 414, and 531, respectively. Sex (P = 0.004), age (P < 0.001), tumor size (P = 0.004), differentiation degree (P = 0.001), and number of N1 LNs examined (P = 0.008) were independent prognostic factors of overall survival. Gender (P = 0.006), age (P = 0.031), tumor size (P = 0.001), differentiation degree (P = 0.001), vascular invasion (P = 0.034), and number of N1 LNs examined (P = 0.007) were independent prognostic factors of disease-free survival. Compared with patients with 0–5 N1 LNs examined, patients with more than 5 N1 LNs examined had better OS (P = 0.015) and had better DFS (P = 0.015) if only a landmark 5-year follow-up was performed.ConclusionIncreasing the number of N1 LN examination might improve the long-term survival of T1-2N0 NSCLC patients. These data indicate that at least 6 N1 nodes examined is an essential part in surgical and pathological management but cannot prove this. This finding should be confirmed in a large, prospective randomized clinical study.

Efficacy analysis of intraoperative radiotherapy in patients with early-stage breast cancer

BackgroundTo analyze the clinical efficacy of intraoperative radiotherapy (IORT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer (BC), and to investigate the relationship between its influencing factors and clinical efficacy and prognosis.MethodsA total of 73 patients with early-stage BC who underwent IORT after BCS in our hospital were selected in this research.ResultsKaplan-Meier survival analysis was used to analyze the related factors of BCS and IORT of disease-free survival (DFS) and overall survival (OS). It was found that only age (χ2 = 14.035, P = 0.003) was statistically positively correlated with the patient’s DFS, and local recurrence and metastasis rate and mortality were higher in patients over 70 years old. Log rank test was used to analyze multiple factors. Only the diameter of the applicator (χ2 = 70.378, P < 0.05) was statistically significant with wound complications, and the larger the diameter, the higher incidence of wound complications. The remaining risk factors did not increase the incidence of wound complications. COX multivariate analysis showed that age was an independent risk factor for DFS rate and the risk factor had no significant effect on the OS rate of patients undergoing IORT after BCS.ConclusionsIORT may be a safe form of treatment for the selected patients with early-stage BC, and can achieve satisfactory esthetic effect. Larger applicator diameters may increase the incidence of wound complications. Age is an independent risk factor for DFS in early-stage BC patients undergoing IORT after BCS.

Clinical relevance of high–intermediate risk endometrial cancer according to European risk classification

ObjectiveRisk models in endometrial cancer define prognosis and indicate adjuvant therapy. One of the currently used classifications was designed in 2016 in collaboration with the European Society of Medical Oncology...

High-dose cytarabine chemotherapy (≥4 g/m2/day) before allogeneic hematopoietic stem cell transplantation for non-core-binding-factor AML in the first complete remission

Benefit of high-dose cytarabine (HD-AraC) for acute myeloid leukemia (AML) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unknown. We retrospectively analyzed data from 79 non-core-binding-factor AML patients who underwent allo-HSCT in their first complete remission (CR1). In univariate analysis, HD-AraC (≥4 g/m2/day) before allo-HSCT improved disease-free survival (DFS) (p = .018), overall survival (OS) (p = .029), and cumulative incidence of relapse (CIR) (p = .033). Four-year DFS, OS, and CIR of patients receiving and not receiving HD-AraC were 79% vs. 49%, 82% vs. 56%, and 18% vs. 42%, respectively. In multivariate analysis, HD-AraC was a positive prognostic factor for DFS (hazard ratio (HR) = 0.36, 95% confidence interval (CI): 0.14–0.88), OS (HR = 0.37, 95% CI: 0.14–0.99), and CIR (HR = 0.38, 95% CI; 0.14–1.0). Our study demonstrates that HD-AraC before allo-HSCT at a dose ≥4 g/m2/day is effective for treating AML patients in CR1.

Abstract 4309: A novel immune prognostic index for the stratification of high-risk patients with early breast cancer

Abstract The prognostic or predictive value of current commercial multigene assays for breast cancer are limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer. Despite the prognostic or predictive significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most current assays. Here, we developed a novel immune gene based-prognostic model to predict the risk of recurrence in high-risk women with early breast cancer. Using public gene expression microarray datasets for breast cancer, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk, and identified the most significant five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) associated with clinical outcome in the clinical and proliferation high-risk (CPH) subgroup. Immune prognostic index based on the combination of the expression of five immune response-related genes and lymph node status was developed to predict the risk of recurrence in high-risk breast cancer patients and its prognostic significance was validated in independent validation datasets. Disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate and low risk in the CPH group. Multivariate analysis demonstrated that the immune prognostic index is an independent prognostic factor for DFS or DMFS. Moreover, c-index showed that the immune prognostic index is superior to clinicopathological variables in predicting the prognosis. Our immune index was also prognostic in independent validation datasets. Our immune prognostic index identified low-risk patients among patients classified as CPH group in all molecular subtypes of breast cancer and may be used to overcome the limitations of the current multigene assay. Citation Format: Hannah Lee, Mi Jeong Kwon, Beom-Mo Koo, Jinil Han, Young Kee Shin. A novel immune prognostic index for the stratification of high-risk patients with early breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4309.

GalNAc-T3 and MUC1, a combined predictor of prognosis and recurrence in solitary pulmonary adenocarcinoma initially diagnosed as malignant solitary pulmonary nodule (≤ 3cm).

The significance of the polypeptide N-acetyl-galactosaminyl transferase-3 (GalNAc-T3) and mucin 1 (MUC1) in solitary pulmonary adenocarcinoma (SPA) initially diagnosed as malignant solitary pulmonary nodule (≤ 3cm), especially as a combined predictor of prognosis and recurrence, was explored in this study. A retrospective analysis of 83 patients with SPA (≤ 3cm), which revealed postoperative pathological diagnosis was lung adenocarcinoma after complete resection. Immunohistochemical staining was used to detect the expression of GalNAc-T3 and MUC1 in primary tumor specimens. The relationship between expression and various clinicopathological factors was analyzed, as well as the effects of patients' overall survival (OS) and disease-free survival (DFS). In all patients, GalNAc-T3 was highly expressed in 53 (63.9%) cases; MUC1 was highly expressed in 31 (37.3%) cases. The GalNAc-T3 expression was correlated with differentiation, pathological risk group, N stage, and TNM stage. The group with high GalNAc-T3 expression and low MUC1 expression (GalNAc-T3Hig/MUC1Low) is correlated to pathological differentiation and has a trend related to the TNM stage. The patients with better differentiation, lower pathological risk group, lower N stage, and GalNAc-T3 high expression had better overall survival, especially the GalNAc-T3Hig/MUC1Low group. Moreover, the moderate differentiation, N3 stage, and GalNAc-T3Hig/MUC1Low group were independent predictive factors for OS. Besides, patients with lower N stage, lower TNM stage, higher GalNAc-T3 expression got better disease-free survival (DFS), especially the GalNAc-T3Hig/MUC1Low group. The GalNAc-T3Hig/MUC1Low group was an independent predictive factor for DFS. In conclusion, GalNAc-T3 and MUC1 were combined predictors of prognosis and recurrence in SPA (≤ 3cm).

Clinico pathological features and treatment outcome of malignant epithelial ovarian tumour

Background: Ovarian cancer is the ninth most common cancer in women and it ranks fifth as the cause of cancer death in women. Epithelial ovarian cancer (EOC) represents the most lethal malignancy of the female genital tract. EOC is typically diagnosed in advanced FIGO (Federation of International Gynaecology and Obstetrics) stages due to lack of symptoms in the earlier stages. So, the aim of this study was to determine the disease free survival (DFS) of EOC after treatment and also to find out the prognostic factors such as age, FIGO stage, histopathological subtypes and grade for recurrence of disease.&#x0D; Methods: A retrospective study was conducted in gynaecological oncology department of National Institute of Cancer Research and Hospital (NICRH), Dhaka. Study period was 02 years from January 2017 to December 2018.Histopathologically confirmed epithelial ovarian malignancy after completion of treatment was included in this study. Non-epithelial ovarian malignancy was excluded from this study.&#x0D; Results: Mean age was 53 yrs (range 25-80 yrs).Final surgical staging (FIGO stage) of disease were as follows stage I; 24 (25.8%), stage II; 18 (19.4%), stage III; 45 (48.4%) and stage IV; 6 (6.5%). Mean follow-up time was 34 months (range 24-60 months). DFS according to FIGO stages were 35 months, 27 months, 25 months and 9 months respectively. DFS based on the complete and incomplete surgical staging were 27 months and 22 months respectively. At univariate analysis, factors significantly associated with decrease DFS and increase recurrence which included age (HR- 1.39 95% CI), stage (HR- 1.22, 95% CI), histopathological type (HR-1.28, 95% CI) and grade of tumor (HR-1.65, 95% CI). At multivariate analysis, FIGO stage (HR-3.9, 95% CI), histopathological type (HR-1.86, 95% CI) and grade (HR-1.11, 95% CI) having an association with decease DFS.&#x0D; Conclusion: Surgical stage was one of the strongest independent prognostic factors of DFS for EOC. Increasing age, histopathology and grade are also independent predictors of decrease DFS in patient with EOC treated with current standard therapy.&#x0D; Bangladesh Med Res Counc Bull 2020; 46(2): 115-119

Adjuvant Transarterial chemoembolization does not influence recurrence-free or overall survival in patients with combined hepatocellular carcinoma and Cholangiocarcinoma after curative resection: a propensity score matching analysis

BackgroundThe prognosis of patients with combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC) is usually poor, and effective adjuvant therapy is missing making it important to investigate whether these patients may benefit from adjuvant transarterial chemoembolization (TACE). We aimed to evaluate the efficiency of adjuvant TACE for long-term recurrence and survival after curative resection before and after propensity score matching (PSM) analysis.MethodsIn this retrospective study, of 230 patients who underwent resection for CHC between January 1994 and December 2014, 46 (18.0%) patients received adjuvant TACE. Univariate and multivariate regression analyses were used to identify the independent predictive factors of survival. Cox regression analyses and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS) between patients who did or did not receive adjuvant TACE.ResultsA total of 230 patients (mean age 52.2 ± 11.9 years; 172 men) were enrolled, and 46 (mean age 52.7 ± 11.1 years; 38 men) patients received TACE. Before PSM, in multivariate regression analysis, γ-glutamyl transpeptidase (γ-GT), tumour nodularity, macrovascular invasion (MVI), lymphoid metastasis, and extrahepatic metastasis were associated with OS. Alanine aminotransferase (ALT), MVI, lymphoid metastasis, and preventive TACE (HR: 2.763, 95% CI: 1.769–4.314, p < 0.001) were independent prognostic factors for DFS. PSM created 46 pairs of patients. Before PSM, adjuvant preventive TACE was not associated with an increased risk of OS (HR: 0.911, 95% CI: 0.545–1.520, p = 0.720) or DFS (HR: 3.345, 95% CI: 1.686–6.638, p = 0.001). After PSM, the 5-year OS and DFS rates were comparable in the TACE group and the non-TACE group (OS: 22.7% vs 14.9%, respectively, p = 0.75; DFS: 11.2% vs 14.4%, respectively, p = 0.06).ConclusionsThe present study identified that adjuvant preventive TACE did not influence DFS or OS after curative resection of CHC.

Prognostic value of nucleotyping, DNA ploidy and stroma in high-risk stage II colon cancer

BackgroundHeterogeneity with respect to recurrence and survival in high-risk stage II colon cancer patients still exists, and further classification is urgently required. This study aimed to ascertain the prognostic value of DNA ploidy, stroma-tumour fraction and nucleotyping in the prognosis of high-risk stage II colon cancer.MethodsA total of 188 high-risk stage II colon cancer patients received radical surgery in Peking University Cancer Hospital, from 2009 to 2015. Status of mismatch repair proteins in tumours was analysed using immunohistochemistry. DNA ploidy, stroma-tumour fraction and nucleotyping were estimated by automated digital imaging systems.ResultsNucleotyping and DNA ploidy were significant prognostic factors, while stroma-tumour fraction were not significantly prognostic in the univariate analysis. In the multivariable model, the dominant contributory factor of disease-free survival was chromatin heterogeneous vs. chromatin homogeneous [HR 3.309 (95% CI: 1.668–6.564), P = 0.001].ConclusionsOur study indicates that nucleotyping is an independent prognostic factor in high-risk stage II colon cancer. Therefore, it may help subdivide patients into different subgroups and give them different strategies for follow-up and treatment in the future.

The optimal time interval between the placement of self-expandable metallic stent and elective surgery in patients with obstructive colon cancer

A bridge to surgery (BTS) after a colonic stent for obstructive colon cancer has not been accepted as a standard treatment strategy. Also, there is no consensus regarding the optimal time interval for BTS. We aimed to identify the optimal timing for BTS after stent placement to decrease the oncologic risk. We retrospectively collected data of 174 patients who underwent BTS after stent placement for stage II or III obstructive colon cancer from five hospitals. We divided the patients into three groups based on the time interval for BTS after stent placement: within 7 days (Group 1), from 8 to 14 days (Group 2), and after 14 days (Group 3). The primary outcome was to compare the oncologic outcomes including overall survival (OS), disease-free survival (DFS), and recurrence rate (RR) among the three groups. Groups 1, 2, and 3 involved 75, 56, and 43 patients, respectively. Postoperative morbidity rates were 17.3%, 10.8%, and 9.3% in Groups 1, 2, and 3, respectively (P = 0.337). RRs were 16.0%, 35.7%, and 30.2% in Groups 1, 2, and 3, respectively (P = 0.029). In multivariate analysis, the time interval for BTS was an independent risk factor for DFS (P < 0.001; HR, 14.463; 95% CI, 1.458–3.255) and OS (P = 0.027; HR, 4.917; 95% CI, 1.071–3.059). In conclusion, the perioperative short-term outcome was not affected by the time interval of BTS. However, elective surgery within 7 days after colonic stent might be suggested to balance the short-term benefits and long-term oncologic risks.

Cervical Cancer in Young Women: Do They Have a Worse Prognosis? A Retrospective Cohort Analysis in a Population of Mexico.

Cervical cancer (CC) is a global problem; it is among the five leading causes of cancer death in women. Several studies have examined the association between age and disease prognosis; however, controversy still exists. The objective of the present study is to determine if age at diagnosis has an impact on overall survival (OS) and disease-free survival (DFS). Retrospective cohort of 2,982 patients with CC treated at the National Cancer Institute of Mexico from 2005 to 2015. We collected demographic, clinical, and treatment data, as well as current status, of 2 groups: women under and over 40 years of age. We calculated OS and DFS rates with Kaplan-Meier estimates. Cox proportional hazards modeling was used to determine risks. The median follow-up time was 26.5 months (percentile [P]25 -P75 , 11-60.23). When comparing DFS, OS, stage, and histologic subtype between young patients <40 and adult patients >40, we did not observe any difference. We found that in both groups, locally advanced and advanced stage, neuroendocrine subtype, hydronephrosis, and positive inguinal lymph nodes increased the risks of death and recurrence. Having been pregnant was identified as protective factor in DFS (hazard ratio, 0.54; 95% confidence interval, 0.04-0.71). We corroborated that age at diagnosis is not a prognostic factor for decreased or increased OS or DFS, and in both groups, the stage, histologic subtype, hydronephrosis, and node involvement were identified as factors adverse to OS and DFS, and pregnancy history was a protective factor in DFS. The present study directly affects everyday clinical practice because it allows us to focus on the most relevant prognostic factors in patients with cervical cancer. When planning treatment and follow-up, clinicians should focus on stage at diagnosis, histologic subtype, hydronephrosis, and distant metastasis instead of patients' age. They should also be aware of any previous pregnancies and poor response, or nonresponse, to treatment, which results in disease progression and persistence. Paying attention to these factors affecting overall survival and disease-free survival will help treat patients better and increase their chances of survival and improve their quality of life.

Evaluation of treatment patterns and prognosis in correlation with age in patients with vulvar cancer: A subset analysis of the AGO-CaRE-1 study.

6090 Background: Despite an increasing incidence with simultaneous decreasing age of onset, the impact of age on prognosis and treatment patterns in primary squamous cell vulvar cancer (VSCC) has not extensively been studied yet. Methods: This is a subgroup analysis of the AGO-CaRE-1 study. Patients (pts) with VSCC (FIGO stage ≥1B), treated at 29 cancer centers in Germany from 1998-2008, were included in a centralized database (n = 1618). In this subgroup analysis pts were analyzed according to age ( &lt; 50yrs (n = 220), 50–69yrs (n = 506), ≥70yrs (n = 521)) with regard to treatment patterns and prognosis. Only pts with documented age, surgical groin staging and known nodal status were included (n = 1247). Median follow-up was 27.5 months. Results: At first diagnosis, women ≥70yrs presented with more advanced tumor stages ( &lt; 0.001), larger tumor diameter ( &lt; 0.001), poorer ECOG status ( &lt; 0.001), higher tumor grading (0.048), as well as a higher rate of nodal involvement ( &lt; 0.001). Older women ≥70yrs showed more commonly HPV negative tumors compared to the other age groups (54% vs. 36.5% in &lt; 50yrs vs. 47.9% in 50-69yrs, p = 0.03). Disease recurrence occurred significantly more often in elderly women (48% vs. 21% in &lt; 50yrs vs. 37.4% in 50-69yrs, p = 0.001). Particularly isolated vulvar recurrence was more frequent in the elderly in comparison to the younger groups (18.2% vs. 15.2% in 50-69yrs vs. 12.7% in &lt; 50yrs, p = 0.001). Age was an independent prognostic factor for disease-free survival (DFS) (HR: 1.7, 95%CI: 1.24-2.46, p = 0.001) with 2-year DFS being 81.1% (&lt; 50yrs), 65.8% (50–69yrs), and 59.3% (≥70yrs), respectively. Elderly women (age group ≥70) had a 221% higher risk for death or recurrence, compared to the youngest group (HR: 3.21, p &lt; 0.001). In a multivariate analysis ECOG, tumor stage, grading, and receipt of (chemo)radiation were further independent prognostic factors for recurrence. Conclusions: Older women with VSCC present with advanced tumor stages at first diagnosis and have an increased risk of recurrence as well as a decreased 2-year PFS in comparison to younger pts groups. Potential reasons for delayed time of diagnosis could be self-awareness and/or more aggressive tumor biology due to HPV negative disease.

Prognostic value of De Ritis ratio (aspartate transaminase/alanine transaminase) in patients with non-metastatic colorectal carcinoma [izmir oncology group(IZOG) study

e16114 Background: We aimed to assess the prognostic effect of preoperative De Ritis (aspartate aminotransaminase/Alanine aminotransaminase) ratio and pathological variables to find out whether it is an independent prognostic factor in patients with non-metastatic CRC. Methods: We retrospectively evaluated the patients who underwent curative surgery for non-metastatic CRC between 2006 and 2017. The potential prognostic value of De Ritis ratio was assessed by using a ROC curve analysis. The effect of the De Ritis ratio was analyzed by the Kaplan–Meier method and Cox regression hazard models for patients’ disease-free survival (DFS) and overall survival (OS). Results: We had 921 CRC patients in total. The univariate analysis demonstrated that low De-Ritis ratio and several well-established prognostic factors, including well-differentiated tumor,negative lymph node involvement, lymphatic invasion, perineural invasion and surgical margin, left tumor localization and early-stage tumor were good prognostic factors in terms of DFS and OS. On the multivariate analysis, De-Ritis ratio, lymph node involvement, perineural invasion status, surgical margin statusand tumor localization were independent prognostic factors for DFS [ De-Ritis ratio HR 0.468, 95% CI 0.358-0.613,p &lt; 0.001]. We also found that De-Ritis ratio, degree of differentiation, lymphatic invasion status, perineural invasion statusand stage were independent prognostic factors for OS on multivariate analysis [ De-Ritis ratio HR 0.354, 95% CI 0.407-0.702, p &lt; 0.001]. Conclusions: Our study first established a connection between the preoperative De-Ritis ratio and patients undergoing curative resection for non-metastatic colorectal cancer, suggesting that De-Ritis ratio was a simple, inexpensive, and easily measurable marker as a prognostic factor and may help to identify high-risk patients for treatment decisions.

Association of postoperative serum carcinoembryonic antigen (CEA) with disease-free survival in patients with stage III colon cancer: ACHIEVE phase III randomized clinical trial.

4069 Background: ACHIEVE, as part of the IDEA collaboration, was a multicenter trial randomizing patients with stage 3 resected colon cancer to either 3 versus 6 months of adjuvant FOLFOX/CAPOX. We previously reported that the hazard ratios (HRs) in disease-free survival (DFS) of 3 versus 6 months duration according to risk stage (low-risk [T1-3 and N1] or high-risk [T4 or N2]) and regimen (FOLFOX or CAPOX) as well as in overall population were consistent with those observed in the whole IDEA. This study aimed to clarify the significance of post-operative serum carcinoembryonic antigen (CEA) on DFS in stage 3 colon cancer. Methods: Eligibility included post-operative serum CEA value of ≤10 ng/ml at registration in the ACHIEVE trial, which enrolled 1313 patients between 2012 and 2014, out of whom 1291 pts were the modified ITT (mITT) population and used in this study. The cutoff values of CEA analyzed for prognostic analyses were the median value (1.8 ng/ml) in the mITT, the upper limit of normal (ULN) level (5.0 ng/ml), and the half of ULN (2.5 ng/ml). The association of post-operative CEA with DFS were measured by Cox regression analyses. Results: Of the 3 cutoff values, the ULN (5.0 ng/ml) was associated with DFS more strongly than the median (1.8 ng/ml) or half of ULN (2.5 ng/ml), with a HR of 1.75 (95%CI, 1.24-2.46) (Table). The 99 patients (7.7%) were identified as the CEA &gt; ULN and 1192 (92.3%) as &lt; ULN. In univariate analysis, regimen (CAPOX or FOLFOX), ECOG PS (0 or 1), T factor (T1-3 or T4), N factor (N1 or N2-3) and CEA ( &lt; ULN or &gt; ULN) were significantly associated with DFS. Multivariate Cox regression identified CEA &gt; ULN as an independent poor risk factor (HR = 1.45; 95%CI, 1.03-2.05). Shorter DFS in patients with CEA &gt; ULN than in those with CEA &lt; ULN was consistently observed in each subgroup of baseline factors, including treatment duration, regimen, age, gender, PS, T-stage, N-stage, no of lymph nodes examined, and tumor location; no interaction was observed between CEA and these factors. Conclusions: Post-operative serum CEA is also a strong prognostic factor for DFS in stage 3 colon cancer. Clinical trial information: 000008543 . [Table: see text]

Next generation sequencing reveals CCNE1 amplification as an independent prognostic factor for triple negative breast cancer (TNBC) patients.

558 Background: Triple negative breast cancer (TNBC) has the worst prognosis among breast cancer due to the heterogeneity as well as lack of better therapeutic approach. It remains controversial whether BRCA status is the predictor of survival in TNBC. Besides, both germline and somatic mutation may contribute to the prognosis. This study is to explore the potential predictors and therapeutic targets based on genetic data and clinicopathological parameters. Methods: Seventy-five TNBC patients were enrolled with approximately 2:1 based on BRCA status. Genetic data was analysed by comprehensive genomic profiling 508 key cancer related genes. DAVID was applied to perform pathway enrichment analysis of significant enriched genetic alterations. Cox regression model was applied to evaluate disease-free survival (DFS) and overall survival (OS). Immuno-chemistry (IHC) was used to validate clinically meaningful genetic alteration. Results: In this study, 27 germline mutations were detected, including 26 homologous recombination repair (HRR) pathway gene mutations and 1 mismatch repair gene mutation among them 16 BRCA1 mutations and 5 BRCA2 mutations were found. Germline HRR including BRCA1/2 mutation marginally affected DFS ( p = 0.0624 and 0.15, respectively). We found 480 somatic genetic alterations including 110 copy number variations (CNV). The median value of TMB was determined to be 4.1 Muts/Mb which divided 74 TNBC patients into TMB-low (TMB-l) and TMB-high (TMB-h) group. TMB-l group had inferior DFS to TMB-h ( p = 0.0457). CCNE1 (with 5% frequency) copy number gain was specifically enriched in TMB-l group but mutually exclusive with BRCA1/2 mutation. TNBC with CCNE1 gain displayed worse DFS ( p&lt; 0.0001). Cox multivariate regression analysis indicated CCNE1 gain was an independent risk factors for DFS [HR = 13.48 (95% CI 2.62-69.23), p= 0.002)]. Pathway analysis indicated CCNE1 harmed prognosis through regulation of transcription in G1/S phase. Expression of cyclin E1 was validated by IHC, which would be presented later. Conclusions: Comprehensive genomic profiling disclosed various potential prognostic markers for TNBC by integrating clinical characters. Especially, amplified CCNE1 may be a potential prognostic marker and therapeutic target. [Table: see text]

The prognostic value of lymph node ratio in Medullary thyroid carcinoma: A multi-center study

IntroductionThe lymph node ratio (LNR), which represents the proportion of metastatic lymph nodes resected, has been found to be a prognostic variable in several cancers, but data for Medullary thyroid carcinoma (MTC) are sparse. The aim of this study was to determine the value of the LNR in predicting outcome in patients with MTC. Materials and methodsA retrospective multicenter study design of 107 patients with MTC who underwent total thyroidectomy with neck dissection between 1984 and 2016. The association of LNR with patient and tumor characteristics and prognostic factors was evaluated. ResultsStudy population consisted of 53.3% female, mean age at diagnosis was 50.3 ± 18.4 years; 16.8% had inherited MTC. LNR was positively correlated with tumor size (p = 0.018) and inversely correlated with age at diagnosis (p = 0.024). A higher LNR was associated with extrathyroidal extension (p < 0.001), multifocality (p = 0.001), bilateral tumor (p = 0.002), distant metastases (p < 0.001), and tumor recurrence (OR = 14.7, p < 0.001). LNR was also correlated to postoperative calcitonin levels (p < 0.001) and carcinoembryonic antigen (p = 0.011). LNR >0.1 was associated with shorter disease-specific survival in patients at risk: tumor larger than 20 mm at diagnosis (p = 0.013), sporadic MTC (p = 0.01), and age above 40 years at diagnosis (p = 0.004). Cox multivariate survival analysis revealed LNR as the only significant independent factor for disease free survival (p = 0.005). ConclusionsThis study showed that LNR correlates well with patient and tumor characteristics and prognostic variables. We suggest that LNR should be considered an important parameter for predicting outcome in MTC.