Independent Predictors Of Worse Disease-free Survival Research Articles

Gastric cancer with peritoneal metastases: a single center outline and comparison of different surgical and intraperitoneal treatments.

Gastric cancer with peritoneal metastasis (GCPM) has an unfavourable prognosis. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are promising treatment options that have been shown to improve survival. The aim of this study was to assess the impact of different treatments such as systemic chemotherapy, systemic chemotherapy + PIPAC, and CRS + HIPEC in patients with GCPM. This single-centre retrospective study included 82 patients with GCPM treated between January 2016 and June 2021. After first-line chemotherapy, depending on disease response and burden, the patients were divided into three treatment groups: chemotherapy alone, chemotherapy + PIPAC, and CRS + HIPEC. The primary outcome was overall survival (OS) from diagnosis, which was compared among the treatment groups. Thirty-seven (45.1%) patients were administered systemic chemotherapy alone, 25 (30.4%) received chemotherapy + PIPAC, and 20 (24.4%) underwent CRS + HIPEC. The CRS + HIPEC group had better OS (median 24 months) than the PIPAC group (15 months, p = 0.01) and chemotherapy group (5 months, p = 0.0001). Following CRS + HIPEC, the postoperative grade 3-4 complication rate was 25%, and no postoperative in-hospital deaths occurred. The median disease-free survival (DFS) was 12 months. Multivariate analysis identified peritoneal carcinomatosis index (PCI) > 7 as an independent predictor of worse DFS. No independent predictors of OS were identified. Among patients with GCPM, we identified a highly selected population with oligometastatic disease. In this group, CRS + HIPEC provided a significant survival advantage with an acceptable major complication rate compared with other available therapies (systemic chemotherapy alone or in combination with PIPAC).

Preoperative inflammatory markers as prognostic predictors after hepatocellular carcinoma resection: data from a western referral center

BackgroundRecent studies from eastern centers have demonstrate an association between inflammatory response and long-term outcomes after hepatocellular carcinoma (HCC) resection. However, the prognostic impact of inflammatory markers in western patients, with distinct tumor and epidemiologic features, is still unknown.AimTo evaluate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as their impact according to tumor size (< 5 cm, 5–10 cm, > 10 cm) in patients undergoing HCC resection with curative intent.MethodsOptimal cut-off values for NLR, PLR, and MLR were determined by plotting the receiver operator curves. Overall survival (OS) and disease-free survival (DFS) curves were calculated using the Kaplan–Meier method and compared using the log-rank test. The Cox method was used to identify independent predictors of OS and DFS.ResultsIn total, 161 consecutive adult patients were included. A high NLR (> 1.715) was associated with worse OS (P = 0.018). High NLR (> 2.475; P = 0.047) and PLR (> 100.25; P = 0.028) were predictors of short DFS. In HCC < 5 cm, MLR (> 1.715) was associated with worse OS (P = 0.047). In the multivariate analysis, high PLR was an independent predictor of worse DFS [hazard ratio (HR) 3.029; 95%CI 1.499–6.121; P = 0.002].ConclusionInflammatory markers are useful tools to predict long-term outcomes after liver resection in western patients, high NLR was able to stratify subgroups of patients with short OS and DFS, an increased PLR was an independent predictor of short DFS, while high MLR was associated with short OS in patients with early HCC.

Prognostic significance of volume-based 18F-FDG PET/CT parameters and correlation with PD-L1 expression in patients with surgically resected lung adenocarcinoma.

The aim of this study was to retrospectively analyze 18F-FDG positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic variables, programmed death-ligand 1 (PD-L1) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) tumor expression, and other factors as predictors of disease-free survival (DFS) in patients with lung adenocarcinoma (LUAD) (stage IA–IIIA) who underwent surgical resection. We still lack predictor of immune checkpoint (programmed cell death-1 [PD-1]/PD-L1) inhibitors. Herein, we investigated the correlation between metabolic parameters from 18F-FDG PET/CT and PD-L1 expression in patients with surgically resected LUAD.Seventy-four patients who underwent 18F-FDG PET/CT prior to treatment were consecutively enrolled. The main 18F-FDG PET/CT-derived variables were primary tumor maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Surgical tumor specimens were analyzed for PD-L1 and p-STAT3 expression using immunohistochemistry. Correlations between immunohistochemistry results and 18F-FDG PET/CT-derived variables were compared. Associations of PD-L1 and p-STAT3 tumor expression, 18F-FDG PET/CT-derived variables, and other factors with DFS in resected LUAD were evaluated.All tumors were FDG-avid. The cutoff values of low and high SUVmax, MTV, and TLG were 12.60, 14.87, and 90.85, respectively. The results indicated that TNM stage, PD-L1 positivity, and high 18F-FDG PET/CT metabolic volume parameters (TLG ≥90.85 or MTV ≥14.87) were independent predictors of worse DFS in resected LUAD. No 18F-FDG metabolic parameters associated with PD-L1 expression were observed (chi-square test), but we found that patients with positive PD-L1 expression have significantly higher SUVmax (P = .01), MTV (P = .00), and TLG (P = .00) than patients with negative PD-L1 expression.18F-FDG PET/CT metabolic volume parameters (TLG ≥90.85 or MTV ≥14.87) were more helpful in prognostication than the conventional parameter (SUVmax), PD-L1 expression was an independent predictor of DFS in patients with resected LUAD. Metabolic parameters on 18F-FDG PET/CT have a potential role for 18F-FDG PET/CT in selecting candidate LUAD for treatment with checkpoint inhibitors.

Abstract PS6-53: Higher clinical lymph node stage predicts worse survival in patients with breast cancer who achieve a pathologic complete response after neoadjuvant chemotherapy

Abstract Background: Despite patients with breast cancer who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) generally demonstrate improved survival, some of these patients will develop breast cancer recurrence. Identification of factors associated with recurrence in patients with pCR after NAC would be helpful to optimize treatment strategies in breast cancer. In this study, we aim to particularly explore the factors associated with the prognosis of this patient population.Methods: Data of patients from three tertiary hospitals and treated with NAC between 2005 and 2019 were retrospectively collected. A pCR was defined as no invasive tumor in the breast and no tumor in the lymph node (ypT0/is, ypN0). Factors associated with pCR were analyzed using univariable and multivariable logistic regression analyses. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The prognostic value of clinicopathological factors regarding DFS and OS were determined by univariable and multivariable Cox regression analyses.Results: A total of 897 patients were used for the analysis, including 287 patients with a pCR and 610 patients without pCR. Clinical TNM stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, Ki67, molecular subtype, NAC regimen and NAC cycles were associated with pCR status, with TNM stage and molecular subtype as independent predictors of pCR. Patients with a pCR had a superior DFS (pCR vs non-pCR, hazard ratio [HR] 0.26 (95% confidence interval [CI] 0.15-0.45, P&amp;lt;0.001) and OS (pCR vs non-pCR, hazard ratio [HR] 0.13 (95% confidence interval [CI] 0.05-0.35, P&amp;lt;0.001). In patients with pCR, clinical T stage, N stage and TNM stage were associated with DFS and OS, with higher N stage as an independent predictor of a worse DFS and OS.Conclusions:Clinical N stage of breast cancer is an independent predictor of worse DFS and OS in patients with a pCR after NAC. Possible this could support treatment escalation in this patient population in the future. Citation Format: Li-Yun Xie, Kun Wang, Yan-Xia Shi, Hai-Lu Chen, Jian-Hao Huang, Yang-Hang Fan, Si-Qi Qiu, Zhi-Yong Wu. Higher clinical lymph node stage predicts worse survival in patients with breast cancer who achieve a pathologic complete response after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-53.

Population-based outcomes by immunosuppressed status in patients undergoing radiotherapy for oropharyngeal cancer

IntroductionThe incidence of immunosuppression in patients with oropharynx head & neck squamous cell carcinoma (SCC) is not well studied. This study evaluates disease characteristics and treatment outcomes in oropharynx SCC in patients with and without immunosuppression. MethodsA retrospective review of all patients treated with radiotherapy for oropharynx SCC at BC Cancer from 2011 to 2016 was performed. Survival outcomes were assessed using Kaplan-Meier methods and competing risk analysis. Multivariate analysis and propensity score matching were performed. ResultsThere were 1077 patients, of which 5.8% (n = 62) had an immunosuppressive medical condition or were taking long-term immunosuppressive medication at diagnosis. Median follow-up was 3.3 years. Three year OS for patients without immunosuppression was 79.5% (95% Confidence Interval [CI] 76.8–82.0%) and for those with immunosuppression was 64.6% (95% CI 50.9–75.3%) (hazard ratio [HR] 1.78, 95% CI 1.18–2.68, p = 0.0062). The three year disease recurrence for patients without immunosuppression was 24.9% (95% CI 22.2–27.7%) and 44.4% (95% CI 31.5–56.6%) for those with immunosuppression (HR 2.12, 95% CI 1.45–3.11, p = 0.0001). Multivariate analysis of disease free survival (DFS) found that active smoking, advanced TNM stage, base of tongue subsite, p16 negative and unknown, no concurrent chemotherapy, higher Charlson Comorbidity Index, and lower radiation dose were also associated with worse DFS (all p < 0.05). Immunosuppressed patients had worse DFS relative to patients without immunosuppression, p < 0.001, HR 1.97 (95% CI 1.33–2.91). ConclusionImmunosuppression was an independent predictor of worse DFS in this large cohort of patients with oropharynx SCC.

The inflammation-related biomarker CXCR7 independently predicts patient outcome after radical prostatectomy

IntroductionThe influence of inflammation on prostate tumor carcinogenesis is currently much better known than with its role in prostate cancer (CaP) progression. We evaluated the prognostic value of epigenetic (HDAC1, HDAC4, H3Ac) and inflammation-related (CXCR4, CXCR7, CXCL12) biomarkers immunoexpression, in radical prostatectomy specimens, from 2 cohorts of CaP patients with long term follow-up. Materials and MethodsFormalin-fixed and paraffin-embedded radical prostatectomy specimens were obtained from the pathology archives of Prof. Doutor Fernando Fonseca Hospital, in Amadora, Portugal and Portuguese Oncology Institute of Porto, in Porto, Portugal, and tissue microarrays were assembled. It was achieved a set of 234 patients submitted to radical retropubic prostatectomy between January 2000 and December 2005. Immunohistochemistry was used for evaluation of protein expression of epigenetic and inflammation-related markers. Nuclear staining was assessed using digital image analysis. Study outcomes included disease-specific survival and disease-free survival (DFS). Statistical analysis was tabulated using SPSS version 23.0. Hazard ratios (HRs) and survival curves were estimated using Cox-regression and Kaplan-Meyer models, respectively. Statistical significance was set at P < 0.05. ResultsComplete follow-up data was available for 234 patients and median follow-up time was 164 [11–218] months. Patients with higher CXCR4 immunoexpression experienced significantly worse disease-specific survival compared to patients with low expression (HR = 1.016, 95% CI: 1.002–1.031). The same happened with CXCL12 (HR = 0.546 95% CI: 0.322–0.926) and H3Ac (HR = 1.015, 95% CI: 1.001c1.029). In what concerns to DFS, patients with higher expression of CXCR4 and CXCR7 were significantly more prone to experience disease recurrence (HR = 1.003, 95% CI: 1.000–1.005 and HR = 1.111, 95% CI:1.032–1.196, respectively). When adjusted to pTStage and WHO Grade Groups, CXCR7 maintained independent impact on DFS (HR = 1.119, 95% CI: 1.032–1.214). ConclusionsThe interplay between inflammation and epigenetics and its impact in CaP outcome deserves further studies in the future. CXCR7 shows an independent predictor for worse DFS after radical prostatectomy, and could provide important prognostic information for patient management after radical prostatectomy.

Tumor invasion front morphology: a novel prognostic factor for intrahepatic cholangiocarcinoma.

To explore the prognostic value of the morphology of tumor invasion front (TIF) in Intrahepatic Cholangiocarcinoma (ICC). Seventy-four ICC patients with complete clinicopathological data and follow-up information were enrolled in our study. The most typical morphology of TIF of each case will be classified as low-grade group or high-grade group after evaluation by two pathologists. The clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. A total of 26 (35.3%) patients were assigned to low-grade group, while 48 (64.7%) patients were assigned to high-grade group. High-grade group was associated with higher CA19-9 (p=0.032), poor differentiation (p=0.050), larger tumor diameter (p=0.016), advanced T staging (p=0.048), and higher incidence of lymph node (LN) metastasis (0.014). No significant associations were found in demographic and clinical characteristics between the two groups. On multivariable analysis, high-grade group was a significant independent predictor of worse DFS (HR=0.433, 95% CI=0.235-0.800, p=0.002) and OS (HR=0.363, 95% CI=0.187-0.704, p=0.003). High-grade morphology of TIF was an independent prognostic factor of ICC.

Outcome after pancreatectomy for neuroendocrine neoplams according to the WHO 2017 grading system: A retrospective multicentric analysis of 138 consecutive patients

The aim of this study was to evaluate the new World Health Organization (WHO) 2017 grading system and the others clinicopathological factors in pancreatic neuroendocrine tumor (panNET) operated patients. Histological staging was based on the WHO 2017 grading system. Outcome after surgery and predictors of overall survival (OS) and disease free survival (DFS) were evaluated. A total of 138 patients underwent surgical resection with a severe morbidity and mortality rates of 14.5% and 0.7% respectively. Five years OS differed according to WHO 2017: 95% among 58 patients with NETG1, 82% in 68 patients with NETG2, 35% in 7 patients with NETG3 and 0% in 5 patients with NECG3 (P<0.0001). Independent predictors of worse OS were age>60 y.o (P=0.014), synchronous metastasis (P=0.005) and WHO 2017 with significant differences between NETG1 versus NETG2 (P=0.005), NETG3 (P<0.001) and NECG3 (P<0.001). Independent predictors of worse DFS were symptomatic NET (P=0.038), pN+ status (P=0.027) and WHO 2017 with significant differences between NETG1 versus NETG3 (P=0.014) and NECG3 (P=0.009). The WHO 2017 grading system is a useful tool for patient prognosis after panNET resection and the tailoring of therapeutic strategy. Surgery could provide good results in NETG3 patients.

The Impact of a Multivisceral Resection and Adjuvant Therapy in Locally Advanced Colon Cancer

BackgroundMultivisceral resection for locally advanced colon cancer is mandatory to achieve complete tumor resection. We aimed to determine if local multivisceral resections (LMR) for pT4 and pT3 tumors impact perioperative and long-term oncological outcomes. MethodsAll stage II or III colon cancer patients who had surgery between 2004 and 2014 were identified. We analyzed patients with non-multivisceral resections (NMR) for pT4 tumors vs. pT4-LMR. In addition, outcomes were compared to both NMR and LMR pT3 patients. ResultsLMR was performed in 55 (29.7%) of all patients with pT4 tumors and in 48 (8.9%) of all patients with pT3 tumors. The most commonly involved areas of extension were the abdominal wall and the small intestine. Transverse colon cancer was correlated with LMR. Morbidity rates were comparable between NMR and LMR, with the exception of higher rates of blood transfusion and postoperative ileus. Over one third of all pT4-NMR patients developed recurrent disease, which was higher compared to all other groups. Subsequently, overall and disease-specific survival, as well as disease-free survival (DFS), was worse for pT4-NMR, even after adjustment for pTN-staging, adjuvant therapy, and R0 resection. Furthermore, when analyzing only curative resections, radial margin < 1 cm along with nodal disease was independent predictor for worse DFS. Long-term outcomes were comparable between pT4-LMR and pT3 patients. ConclusionsMultivisceral resection for locally advanced colon cancer preserves long-term oncological outcomes without increased postoperative morbidity. Moreover, LMR in pT3 tumors does not contribute to postoperative morbidity. Our study underlines the feasibility and importance of performing LMR when locally advanced cancer is suspected.

Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas

ObjectivesDespite successful surgery, 30–50% of patients with resectable non-small cell lung cancer develop tumor recurrence within 5 years of surgery. Materials and methodsIn this prospective study, we performed CTC enumerations in 40 patients with non-metastatic lung adenocarcinoma (NMLA) using a size-based microfilter. Additionally, cfDNA isolated from plasma was analyzed in 35 out of 40 patients. ResultsCTCs were identified in 15 out of 40 patients (37.5%) with a range of 1–44 cells, whereas mutated cfDNA was only detected in 3 out of 35 patients (8.6%). Disease-free survival (DFS) was significantly associated with CTC positivity (log-rank p=0.025), grading (log-rank p=0.019), tumor stage (log-rank p=0.025) and lymph node status (log-rank p=0.029). Multivariate analysis, including tumor stage and grading, showed that CTC positivity (p=0.006), grading (0.039) and tumor stage (p=0.022) were independently associated with DFS. ConclusionOur study found that microfilter-based CTC enumeration in NMLA patients is an independent predictor of worse DFS. The used NGS-based cfDNA characterization had limited sensitivity to be clinically informative in our study cohort. CTC assessment before surgery can thus identify NMLA patients at high risk of disease recurrence.

Cytokeratin-based assessment of tumour budding in colorectal cancer: analysis in stage II patients and prospective diagnostic experience.

Tumour budding in colorectal cancer is an important prognostic factor. A recent consensus conference elaborated recommendations and key issues for future studies, among those the use of pan‐cytokeratin stains, especially in stage II patients. We report the first prospective diagnostic experience using pan‐cytokeratin for tumour budding assessment. Moreover, we evaluate tumour budding using pan‐cytokeratin stains and disease‐free survival (DFS) in stage II patients. To this end, tumour budding on pan‐cytokeratin‐stained sections was evaluated by counting the number of tumour buds in 10 high‐power fields (0.238 mm2), then categorizing counts as low/high‐grade at a cut‐off of 10 buds, in two cohorts. Cohort 1: prospective setting with 236 unselected primary resected colorectal cancers analysed by 17 pathologists during diagnostic routine. Cohort 2: retrospective cohort of 150 stage II patients with information on DFS. In prospective analysis of cohort 1, tumour budding counts correlated with advanced pT, lymph node metastasis, lymphovascular invasion, perineural invasion (all p < 0.0001), and distant metastasis (p = 0.0128). In cohort 2, tumour budding was an independent predictor of worse DFS using counts [p = 0.037, HR (95% CI): 1.007 (1.0–1.014)] and the low‐grade/high‐grade scoring approach [p = 0.02; HR (95% CI): 3.04 (1.2–7.77), 90.7 versus 73%, respectively]. In conclusion, tumour budding assessed on pan‐cytokeratin slides is feasible in a large pathology institute and leads to expected associations with clinicopathological features. Additionally, it is an independent predictor of poor prognosis in stage II patients and should be considered for risk stratification in future clinical studies.

Aggressive surgical treatment with bony pelvic resection for locally recurrent rectal cancer

BackgroundIn the current era of total mesorectal excision, local relapse remains a main cause of recurrence. Although standard treatment for locally recurrent rectal cancer (LRRC) has not been established, R0 resection represents the only potentially curative treatment. However, extended surgery accompanying bony pelvic resection is technically demanding and is still challenging. MethodsStudied were 35 patients with LRRC who underwent combined resection of bony pelvis between August 2006 and October 2013. Safety and prognostic factors for survival were analyzed. Median follow-up was 33 months. ResultsSacrectomy was performed in 32 patients and 3 patients underwent combined resection of the pubis and ischium. The dominant operative procedure was total pelvic exenteration in 30 (86%) patients. R0 resection was achieved in 27 (77%) patients. No patients died. Pelvic sepsis was the most frequent complication (40%). Recurrence developed in 20 (57%), with the lung the most frequent site (10 patients). Three-year local relapse-free survival (LRFS) and disease-free survival (DFS) were 72.1% and 32.7%, respectively. On multivariate analysis, R1 resection was the only independent risk factor for local recurrence (p = 0.010), and concomitant liver metastasis and initial non sphincter-preserving surgery were independent predictors of worse DFS (p = 0.008 and p = 0.042, respectively). ConclusionsAggressive surgical treatment combined with bony resection for carefully selected patients with LRRC was safe with a high rate of R0 resection and favorable LRFS. However, DFS was not satisfactory even after R0 resection and the main cause was lung metastasis. Preventing distant recurrence might be a key to improve survival.

The outcome and efficacy of adjuvant chemotherapy alone in patients with stage IIIA endometrial carcinoma with solitary adnexal involvement: A retrospective single-institution study

ObjectivesThe appropriate adjuvant therapy for patients with endometrial carcinoma with solitary adnexal involvement is unclear. We conducted a retrospective single-institution study to evaluate the outcome and efficacy of adjuvant chemotherapy alone in this population. MethodsAll patients with endometrial carcinoma who received primary surgical treatment between January 1999 and May 2010 were reviewed. The patients who were diagnosed with stage IIIA disease based only on isolated adnexal involvement and treated with surgical procedures followed by adjuvant chemotherapy alone were included. Demographic, clinicopathologic, treatment and outcome data were collected. Recurrence and survival were analyzed. ResultsAmong 1453 reviewed patients, 67 patients were identified. The median age was 48years. All patients were treated with platinum-based adjuvant chemotherapy, with the majority (36/67, 53.7%) receiving paclitaxel plus carboplatin. The total number of cycles of chemotherapy administered was 305 (median four cycles/person). Most of the chemotherapy related toxicities were mild or moderate. The median follow-up time was 76months. Eight patients experienced recurrence. The majority of initial relapses were distant (7/8, 87.5%), characterized by liver metastases (3/8, 37.5%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 89.6% and 91.9%, respectively. Multivariate analysis confirmed that grade 3 tumor was an independent predictor of worse DFS and OS (HR=5.19, P=0.048; HR=6.55, P=0.037, respectively). ConclusionPatients with stage IIIA endometrial carcinoma with solitary adnexal involvement have favorable outcomes. Adjuvant chemotherapy alone may be effective and feasible for these patients.

Survivin mRNA Level in Blood Predict the Efficacy of Neoadjuvant Chemotherapy in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer.

In a previous study, survivin mRNA expression in non-small cell lung cancer (NSCLC) tissue had been demonstrated to be associated with unfavorable prognosis of patients treated with chemotherapy. In this study, we investigated the survivin mRNA levels in blood of patients with stage IIIA-N2 NSCLC and their association with the efficacy of neoadjuvant chemotherapy (NCT) and disease-free survival (DFS) and overall survival (OS). Blood specimens were collected from 56 patients with stage IIIA-N2 NSCLC before (N0) and after the complete of NCT (N1). Survivin mRNA was measured by real-time quantitative-PCR assay. Receiver operating characteristics curve analysis was undertaken to determine the best cutoff value for survivin mRNA. Results showed that high blood survivin mRNA levels at N0 and N1 were significantly associated with clinical (P = 0.01 and P = 0.008, respectively) and pathologic response (both P = 0.004, respectively). Moreover, the change of blood survivin mRNA levels in these NSCLC patients is associated with the clinical and pathologic response to NCT. Patients with high survivin mRNA levels at N0 and N1 had significantly shorter DFS and OS than those with low survivin mRNA levels (P = 0.021 and P = 0.014, respectively for DFS; P = 0.009 and P = 0.005, respectively for OS). Multivariate analysis demonstrated that high blood survivin mRNA level was an independent predictor for worse DFS and OS in the NSCLC patients receiving NCT. In conclusion, survivin mRNA level in blood from stage IIIA-N2 NSCLC patients receiving NCT is predictive of cancer outcome.

Clinical significances of ErbB family receptors, Myc, and mitogen-activated protein kinase (MAPK) in patients with early-stage non-small cell lung cancer.

e21094 Background: EGFR deregulation has been extensively studied in non small-cell lung cancer (NSCLC), but less is known about the expression and role of other ErbB receptors and their downstream signal transductions. Myc and MAPK are key downstream components of the EGFR pathway and have significant roles in cell survival, proliferation, and growth. The purpose of this study is to determine the prognostic value of EGFR, ErbB2, ErbB3, ErbB4, Myc and MAPK by immunohistochemistry (IHC) in early stage NSCLC. Methods: 109 NSCLC were evaluated: median age was 67 years (range 40–84); Male/Female:93/16; squamous (SCC)/adenocarcinoma (ADC)/BAC/other: 52/36/3/18; smoker/never smoker:100/9, and stage I/II/III:67/17/25. The tumors with ≥10% positive cells were classified positive, further confirmed by Receiver Operating Characteristic (ROC) analysis. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical and biologic variables using Cox model for multivariate analysis Results: EGFR and EbrB3 were associated with SCC (p&lt;0.0001 and p=0.004, respectively) whereas ErbB2 and Myc with ADC (p=0.004 and p&lt;0.0001, respectively) . EGFR and ErbB3 were significantly associated (p=0.003), as well as MAPK and ErbB4 (p=0.02). At a median follow-up of 75 months the contemporary overexpression of EGFR, ErbB2 and MAPK was associated with shorter disease free survival (DFS) (HR=5.4, p=0.002) and overall survival (OS) (HR=8.9, p&lt;0.0001). At multivariate analysis adjusting for stage, the co-expression of EGFR, ErbB2 and MAPK was an independent predictor for worse DFS and OS (HR=5.7, p=0.004; HR=8.67, p&lt;0.001, respectively). Conclusions: Our results suggest that in early stage NSCLC, the co-expression of EGFR, ErbB2 and MAPK predicted a worse prognosis. ErbB3, ErbB4 and Myc were not prognostic factors. Such features may have important implications for future targeted therapies. We thank Italian Association for Cancer Research (AIRC) for supporting the study.

Abstract P3-10-10: Progesterone Receptor-Negative Status Predicts Poorer Outcomes in Estrogen Receptor-Positive Patients Treated with Selective Estrogen Receptor Modulators

Abstract Introduction: While estrogen receptor (ER) status has been used as the primary factor influencing the use of selective estrogen receptor modulators (SERMs), a number of ER-positive patients will relapse on this therapy. It has been postulated that SERM-resistance may be modulated by aberrant growth factor signaling, for which progesterone receptor (PR) status may be a surrogate. PR status, however, is frequently not considered as a strong prognostic or predictive marker in ER-positive patients. We sought to define the effect of PR-status on outcomes in such patients treated with SERMs. Methods: The North American Fareston versus Tamoxifen Adjuvant (NAFTA) Trial is an investigator-initiated, multicenter, prospective trial that randomized patients with resected hormone-receptor positive breast cancers to receive either adjuvant tamoxifen (20 mg po daily) or toremifene (60 mg po daily) for five years. Between July 1998 and December 2002, 1692 ER-positive positive patients were randomized. PR was missing for 15 patients. The remaining 1677 (1424 PR-positive and 253 PR-negative) patients formed the cohort of interest for this analysis. The impact of PR status on overall (OS) and disease-free survival (DFS) was assessed using Kaplan Meier and Cox Proportional Hazards modeling. Results: The median patient age was 67 (range; 41-100) with a median tumor size of 1.2 cm (range; 0.01-14.00 cm). PR-positive status was correlated with node-negative disease (91.3% vs. 87.0%, p=0.035) and low grade tumors (34.9% vs. 27.7%, p=0.009), but was not associated with tumor size (p=0.533) or patient age (p=0.067). With a median follow-up of 59 months, the 5-year actuarial OS and DFS of PR-negative patients was significantly worse than that of PR-positive patients (88.5% vs. 94.3%, p=0.009 and 86.1% vs. 92.5%, p=0.003, respectively). Controlling for tumor size, grade and lymph node status, PR-negative status continued to predict worse DFS (OR=1.561; 95% CI: 1.013-2.406, p=0.043), although it lost significance in terms of OS (OR=1.619; 95% CI: 0.980-2.674, p=0.060). Conclusion: PR-negative status is an independent predictor of worse DFS in ER-positive patients treated with SERMs. These data support the hypothesis that PR-negative status may signal a higher rate of SERM-resistance, and should be considered in adjuvant therapy decisionmaking. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-10.