Stage IA Patients Research Articles

Treatment of Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): An Analysis from the German Hodgkin Study Group (GHSG)

Introduction: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for about 5% of all HL cases. As compared with classical HL (cHL), NLPHL is characterized by the absence of CD30 and the consistent expression of CD20 on the malignant lymphocyte predominant (LP) cells. Given a more indolent clinical course, especially early-stage NLPHL is often treated less aggressive than classical HL (cHL). In stage IA patients, radiotherapy (RT) alone is applied at most institutions. However, this clinical practice is not based on data from prospective clinical trials with sufficient follow-up. To shed more light on the optimal treatment of stage IA NLPHL, we performed an analysis including patients with long-term follow-up treated within German Hodgkin Study Group (GHSG) clinical trials.Patients: A total of 256 stage IA NLPHL patients treated within 7 prospective GHSG studies between 1988 and 2009 were included in the analysis. Treatment consisted of combined-modality treatment (CMT) (n=72), extended-field RT (EF-RT) (n=49), involved-field RT (IF-RT) (n=108) or four weekly doses of the anti-CD20 antibody rituximab (n=27).Results: The median age at NLPHL diagnosis was 38.5 years (range: 17-75); 194/256 (75.8%) patients were male and 62/256 (24.2%) patients were female. Median follow-up for the whole patient group was 91 months (98 months for CMT, 118 months for EF-RT, 87 months for IF-RT, 49 months for rituximab). All patients responded to treatment irrespective of the treatment modality applied. At 8 years, progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 94.5% for CMT, 84.3% and 95.7% for EF-RT and 91.9% and 99.0% for IF-RT; 4-year PFS and OS rates for patients treated with rituximab were 81.0% and 100%. Seventeen patients developed a second malignancy in the course of follow-up (8 after CMT, 3 after EF-RT, 4 after IF-RT, 2 after rituxmab). Nine of these second malignancies were solid tumors (4 after CMT, 2 after EF-RT, 1 after IF-RT, 2 after rituximab) and 8 were hematologic malignancies (4 after CMT, 1 after EF-RT, 3 after IF-RT, none after rituximab). A total 12 deaths occurred. The most common cause of death was cardiac failure (n=3). Only one patient died from NLPHL.Conclusion: Based on this large analysis with long-term follow-up, IF-RT should be the standard of care for stage IA NLPHL. Treatment with single agent rituximab is associated with an increased event rate when compared with IF-RT and should therefore not be routinely used in stage IA NLPHL patients. However, given the shorter follow-up in comparison with CMT, EF-RT and IF-RT, final conclusions regarding rituximab especially in terms of treatment-related late sequelae cannot yet be drawn. Addition of chemotherapy does not improve the excellent outcome achieved with RT alone. DisclosuresOff Label Use: Rituximab in NLPHL.

The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts.

We previously developed a prognostic classifier using the expression levels of BRCA1, HIF1A, DLC1, and XPO1 that identified stage I lung adenocarcinoma patients with a high risk of relapse. That study evaluated patients in five independent cohorts from various regions of the world. In an attempt to further validate the classifier, we have used a meta-analysis-based approach to study 12 cohorts consisting of 1,069 tumor-node-metastasis stage I lung adenocarcinoma patients from every suitable, publically available dataset. Cohorts were obtained through a systematic search of public gene expression datasets. These data were used to calculate the risk score using the previously published 4-gene risk model. A fixed effect meta-analysis model was used to generate a pooled estimate for all cohorts. The classifier was associated with prognosis in 10 of the 12 cohorts (P < 0.05). This association was highly consistent regardless of the ethnic diversity or microarray platform. The pooled estimate demonstrated that patients classified as high risk had worse overall survival for all stage I [HR, 2.66; 95% confidence interval (CI), 1.93-3.67; P < 0.0001] patients and in stratified analyses of stage IA (HR, 2.69; 95% CI, 1.66-4.35; P < 0.0001) and stage IB (HR, 2.69; 95% CI, 1.74-4.16; P < 0.0001) patients. The 4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors. Our results suggest that the 4-gene classifier may assist clinicians in decisions about the postoperative management of early-stage lung adenocarcinoma patients.

Expression Profiles and Clinicopathologic Features in Early Resected Non-small-cell Lung Cancer

Expression Profiles and Clinicopathologic Features in Early Resected Non-small-cell Lung Cancer

Impact of adjuvant chemotherapy for stage I ovarian carcinoma with intraoperative tumor capsule rupture.

Adjuvant chemotherapy is generally recommended for early stage epithelial ovarian cancer. However, it remains uncertain which histological subtypes and substages of stage I disease should receive adjuvant chemotherapy. The objective of this study is to determine the impact of chemotherapy among stage I epithelial ovarian cancer. Of the 267 patients with stage I epithelial ovarian cancer analyzed in this study, 152 patients received adjuvant chemotherapy (AC-positive group) and 115 patients did not (AC-negative group). Survival analysis was retrospectively performed to determine the effectiveness of adjuvant chemotherapy in stage I epithelial ovarian cancer patients. Recurrence was observed in 14 patients in the AC-negative group and 20 patients in the AC-positive group. There were no statistically significant differences in disease-free survival (DFS) and overall survival between the two groups. In stage IA and IB patients, there was no statistically significant difference in DFS and overall survival based on adjuvant chemotherapy status. However, in patients with intraoperative tumor capsule rupture, the AC-positive group had significantly better DFS than the AC-negative group (P = 0.01). Patients with clear cell carcinoma who received adjuvant chemotherapy had better DFS than patients who did not (P = 0.004). Adjuvant chemotherapy may not be necessary for patients with stage IA or IB epithelial ovarian cancer, but may be beneficial for clear cell carcinoma patients with intraoperative tumor rupture.

Detection of non-aggressive stage IA lung cancer using chest computed tomography and positron emission tomography/computed tomography.

In contrast to lung cancer with ground-glass opacity, the radiological investigation of solid lung cancer has not been well examined. The aim of this study was to explore chest computed tomography (CT) and positron emission tomography (PET)/CT findings with regard to outcomes after lung cancer surgery in order to radiologically classify clinical stage IA lung cancers by tumour aggressiveness. Three hundred and fifteen clinical stage IA patients were analysed. Four groups were defined by tumour solidity on CT and by the standardized uptake value (SUV) index on PET-CT (tumour maximum SUV/mean right liver lobe SUV). We analysed the association between radiological findings and both pathological invasiveness and postoperative outcome. Group A (n = 84) had an SUV index <1.0 and non-solid tumours, Group B (n = 24) had an SUV index <1.0 and solid tumours, Group C (n = 54) had an SUV index ≥1.0 and non-solid tumours, while Group D (n = 153) had an SUV index ≥1.0 and solid tumours. Invasive lung cancer was found in 2/84 (2.4%) patients in Group A, 1/24 (4.2%) in Group B, 13/54 (24.1%) in Group C and 58/153 (37.9%) in Group D (P < 0.01). The 5-year recurrence-free rate was 100% in Groups A and B, 90.3% in C and 65.7% in D (P < 0.01). The cancer-specific survival rate was 100% in A and B, 94.6% in C and 81.7% in D (P < 0.01). The present results suggest that preoperative PET/CT and thin-section CT findings provide important information for a selection of surgical procedures for clinical stage IA lung cancers. In clinical stage IA lung cancers displaying solid or non-solid density in thin-section findings, an SUV index <1.0 may be a better criterion for detecting non-aggressive lung cancer even in solid lung cancers.

Important Factors Affecting Adjuvant Treatment Decision in Stage IA Breast Cancer Patients in Turkey

Introduction: In Turkey, the gene expression profile test is not standard, so adjuvant treatment is planned according to clinicopathological factors. Therefore, we retrospectively analyzed important parameters that affect the decision on adjuvant chemotherapy, and also factors related to survival in stage IA breast cancer patients in Turkey. Methods: We retrospectively evaluated 347 stage IA patients. The relationship between the clinicopathological parameters and adjuvant chemotherapy was analyzed. Results: The median age and follow-up time were 52 years (range: 25-86) and 22.6 months (range: 1-113), respectively. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 87.9% and 98.7%, respectively, but the median DFS was not reached. Age, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, and the presence of triple-negative breast tumor (TNBC) were related to DFS, and lymphovascular invasion (LVI), perineural invasion (PNI), HER2 status, the presence of TNBC, and recurrence were related to OS (p < 0.05). Furthermore, age, menopausal status, multicentricity, grade, tumor size, necrosis, ER, the presence of TNBC, and HER2 were found to be related to adjuvant therapy decision (p < 0.05). All these parameters, in addition to LVI and PNI, were independent factors for chemotherapy by logistic regression analysis. Conclusions: In decisions about adjuvant therapy in stage IA breast cancer patients, clinicopathological factors should be kept in mind.

Treatment of stage Ia and Ib mycosis fungoides with psoralen UVA monotherapy: an observational study in tertiary hospitals in the Canary Islands

Mycosis fungoides (MF) is the most common form of primary cutaneous Tcell lymphoma. Psoralen combined with ultraviolet A (PUVA) is a first-line treatment for early-stage disease. This study was conducted to assess the clinical effectiveness of and tolerance to PUVA monotherapy in MF. We retrospectively reviewed the files of patients who received PUVA for stage I disease. The study included 31 patients, of whom 32% presented with stage Ia and 67% with stage Ib disease, and 68% presented with patch and 32% with plaque disease. All patients received treatment three times per week. Complete response (CR) was achieved in 71% of patients. The median cumulative dose of UVA at CR was 211.7J/cm(2) . There was a significant difference in median cumulative dose at CR between patients with plaque and patch disease, respectively, but not between patients with stage Ia and Ib disease. Median disease-free survival (DFS) was 230weeks. Patients with patch disease achieved longer DFS than those with plaque disease (P=0.004), although DFS was similar in stage Ia and Ib patients. Of the patients who received maintenance therapy, 58% relapsed. Univariate analysis showed patch disease to be a predictive factor for CR, but no predictors of relapse were identified. A total of 71% of patients developed clinical adverse reactions. Psoralen with UVA is a safe and effective treatment for early-stage MF. Patch disease responds more favorably than plaque disease and is associated with a longer period of DFS. Maintenance treatment does not appear to reduce recurrence. Current evidence suggests that the proposed revision to the classification of MF, which takes into account the extent and type of disease, more accurately predicts response to PUVA.

Incidence and clinical outcomes of non-endometrioid carcinoma of endometrium: Siriraj Hospital experience.

To study the incidence of non-endometrioid carcinoma of endometrium and compare the clinical characteristics and treatment outcomes with endometrioid carcinoma patients. This study included 236 patients with endometrial carcinoma at Siriraj Hospital whom were diagnosed and treated from 2003 through 2006. The clinical characteristics, pathological features, treatment and clinical outcomes were collected from the medical records. The 5-year survival was calculated according to 2009 FIGO staging. Non-endometrioid carcinoma of endometrium accounted for 10.2% of all endometrial carcinomas (24/236 patients). The 5 -year survival rate was significantly lower in the non-endometrioid group compared to the endometrioid group (77.3% vs 96%, p<0.001) and clinical data pointed to greater malignancy. Non-endometrioid carcinoma of endometrium is relative rare but is more aggressive, has more distant metastasis at diagnosis with a worse survival rate than endometrioid carcinoma. Only patients in stage IA with no residual disease on a hysterectomy specimen may not need adjuvant treatment.

Clinical outcomes and changes in lung function after segmentectomy versus lobectomy for lung cancer cases

We compared the clinical outcomes and changes in pulmonary function test (PFT) results after segmentectomy or lobectomy for non-small cell lung cancer. The retrospective study included 212 patients who had undergone segmentectomy (group S) and 2336 patients who had undergone lobectomy (group L) from 1997 to 2012. The follow-up and medical record data were collected. We used all the longitudinal PFT data within 24 months postoperatively and performed linear mixed modeling. We analyzed the 5-year overall and disease-free survival in stage IA patients. We used propensity score case matching to minimize the bias due to imbalanced group comparisons. During the perioperative period, 1 death (0.4%) in group S and 7 (0.3%) in group L occurred. The hospital stay for the 2 groups was similar (median, 5.0 vs 5.0 days; range, 2-99 vs 2-58). The mean overall and disease-free survival period of those with T1a after segmentectomy or lobectomy seemed to be similar (4.2 vs 4.5 years, P=.06; and 4.1 vs 4.4 years, P=.07, respectively). Compared with segmentectomy, lobectomy yielded marginally significantly better overall (4.4 vs 3.9 years, P=.05) and disease-free (4.1 vs 3.6 years; P=.05) survival in those with T1b. We did not find a significantly different effect on the PFTs after segmentectomy or lobectomy. Both surgical types were safe. We would advocate lobectomy for patients with stage IA disease, especially those with T1b. A retrospective study with a large sample size and more detailed information should be conducted for PFT evaluation, with additional stratification by lobe and laterality.

Primary Ovarian Mucinous Adenocarcinoma of Intestinal Type

This study was aimed to evaluate the clinicopathologic details of primary ovarian mucinous adenocarcinoma and their prognostic significance. The clinicopathologic characteristics of 46 cases of mucinous adenocarcinoma were reviewed. The diagnosis of mucinous adenocarcinoma required the presence of stromal invasion of either the expansile (confluent glandular) pattern or the infiltrative pattern in an area size >10 mm(2). The cases were stratified using different grading methods and different cutoff limits of stromal invasion. Regarding the invasive pattern, 20 cases had the infiltrative pattern only, 8 had both infiltrative and expansile patterns, 7 had the expansile pattern only, and 11 had the expansile pattern with infiltrative microinvasion (area ≤10 mm(2)). The patients with tumors containing the expansile pattern had a younger mean age compared with those with the infiltrative pattern only (42.3 vs. 53.7 yr; P=0.004). On follow-up, 12 patients had tumor recurrence, 9 of whom died of disease. Tumor recurrence was associated with stage ≥II (P<0.001) and infiltrative area >10 mm(2) (P=0.015). Decreased progression-free survival and cancer-specific survival was strongly associated with tumor stage ≥II (P<0.001 for each survival) and infiltrative area >50 mm(2) (P=0.003 and 0.010, respectively). Among 27 stage IA patients, the infiltrative extent (area >50 mm or dimension >20 mm) was the only variable that was significantly associated with recurrence and decreased survival. Tumor grading was not significantly associated with the recurrence risk or the survival. The extent of infiltrative invasion in ovarian mucinous adenocarcinoma may provide additional prognostic value to the tumor stage and the pattern of stromal invasion.

Abstract B35: The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts.

Abstract We previously developed and validated a prognostic classifier using the mRNA expression levels of BRCA1, HIF1A, DLC1, and XPO1. This 4-gene classifier aimed to identify stage I lung adenocarcinoma patients with a high risk of relapse. Our initial study evaluated patients in five independent cohorts from various regions of the world, suggesting that the 4-gene classifier was robust and representative of most lung adenocarcinomas. In an attempt to further validate this classifier, we have used a meta-analysis based approach to study 12 cohorts consisting of 1069 TNM stage I lung adenocarcinoma patients. These cohorts were obtained through a systematic search of public gene expression datasets and all suitable datasets were analyzed. Kaplan-Meier analysis of each cohort showed that the classifier was significantly associated with prognosis in ten of the twelve cohorts (p&amp;lt;0.05). The association was highly consistent across all cohorts regardless of the ethnic diversity or microarray platform and there was no evidence of heterogeneity across all cohorts (I2 = 0.0%, p=0.98). The pooled estimate demonstrated that patients classified as high risk had worse overall survival for all stage I (Hazard Ratio [HR], 2.66; 95% Confidence Interval [CI], 1.93-3.67; P&amp;lt;0.0001) patients and in stratified analyses of stage IA (HR, 2.69; 95%CI, 1.66-4.35; P&amp;lt;0.0001) and stage IB (HR, 2.69; 95%CI, 1.74-4.16; P&amp;lt;0.0001) patients. These results suggest that the 4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors and may assist clinicians in decisions regarding postoperative management of early stage patients. Citation Format: Hirokazu Okayama, Aaron J. Schetter, Teruhide Ishigame, Ana I. Robles, Takashi Kohno, Jun Yokota, Seiichi Takenoshita, Curtis C. Harris. The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B35.

Validation of a Histology-Independent Prognostic Gene Signature for Early-Stage, Non–Small-Cell Lung Cancer Including Stage IA Patients

Patients with early-stage non-small-cell lung carcinoma (NSCLC) may benefit from treatments based on more accurate prognosis. A 15-gene prognostic classifier for NSCLC was identified from mRNA expression profiling of tumor samples from the NCIC CTG JBR.10 trial. In this study, we assessed its value in an independent set of cases. Expression profiling was performed on RNA from frozen, resected tumor tissues corresponding to 181 stage I and II NSCLC cases collected at University Health Network (UHN181). Kaplan-Meier methodology was used to estimate 5-year overall survival probabilities, and the prognostic effect of the classifier was assessed using the log-rank test. A Cox proportional hazards model evaluated the signature's effect adjusting for clinical prognostic factors. Expression data of the 15-gene classifier stratified UHN181 cases into high- and low-risk subgroups with significantly different overall survival (hazard ratio [HR] = 1.92; 95% confidence interval [CI], 1.15-3.23; p = 0.012). In a subgroup analysis, this classifier predicted survival in 127 stage I patients (HR = 2.17; 95% CI, 1.12-4.20; p = 0.018) and the smaller subgroup of 48 stage IA patients (HR = 5.61; 95% CI, 1.19-26.45; p = 0.014). The signature was prognostic for both adenocarcinoma and squamous cell carcinoma cases (HR = 1.76, p = 0.058; HR = 4.19, p = 0.045, respectively). The prognostic accuracy of a 15-gene classifier was validated in an independent cohort of 181 early-stage NSCLC samples including stage IA cases and in different NSCLC histologic subtypes.

Sublobectomy versus lobectomy for stage IA (T1a) non-small-cell lung cancer: a meta-analysis study.

BackgroundAlthough lobectomy is considered the standard surgical treatment for the majority of patients with non-small-cell lung cancer (NSCLC), the operation project for patients with stage IA NSCLC (T1a, tumor diameter ≤2 cm) remains controversial. Sublobectomy is appropriate only in certain patients as many doctors consider it to be overtreatment. We evaluated the five-year overall survival rate of sublobectomy and lobectomy for stage IA NSCLC (T1a, tumor diameter ≤2 cm) through a meta-analysis.MethodsThe five-year overall survival rate (OS) of stage IA (T1a) NSCLC after sublobectomy (including wedge resection and segmentectomy) and lobectomy were compared. We also compared the OS of stage IA (T1a) NSCLC after segmentectomy and lobectomy. The log (hazard ratio, ln (HR)) and its standard error (SE) were used as the outcome measure for data combining.ResultsThere were 12 eligible studies published between 1994 and 2013 in which the total number of participants was 18,720. When compared to lobectomy, there was a statistically significant difference of sublobectomy on OS of stage IA (T1a) NSCLC patients (HR 1.38; 95% confidence interval (95% CI), 1.19 to 1.61; P <0.0001). For the comparison between segmentectomy and lobectomy, there was also a statistically significant difference of segmentectomy alone on OS of stage IA (T1a) NSCLC patients (HR 1.48; 95% CI: 1.27 to 1.73; P <0.00001)ConclusionsWe have concluded that in stage IA (T1a) patients sublobectomy, including segmentectomy and wedge resection, causes a lower survival rate than lobectomy.

Patterns of relapse in stage I–II uterine papillary serous carcinoma treated with adjuvant intravaginal radiation (IVRT) with or without chemotherapy

ObjectiveTo evaluate patterns of relapse in early stage uterine papillary carcinoma (UPSC) patients receiving adjuvant intravaginal radiotherapy (IVRT) with or without chemotherapy. MethodsFrom 1/1996 to 12/2010, 77 women with stage I–II UPSC underwent surgery followed by IVRT (median 21Gy). Stage IA patients without residual disease at surgery were excluded. IVRT and chemotherapy (carboplatin/taxane) was given to 61 (79%) patients and IVRT alone to 16 (21%). The median follow-up was 62months for surviving patients. ResultsOf the 77 patients, 11 (14%) relapsed as follows: vaginal 2 (3%), pelvic 5 (6%), para-aortic 5 (6%), peritoneal 6 (8%), and other distant sites 8 (10%). Of the 5 pelvic relapses, 2 were isolated and were salvaged. In those treated without chemotherapy, only 1/16 developed recurrence (mediastinal). The 5-year vaginal, pelvic, para-aortic, peritoneal, and distant recurrence rates were 2.7% (C.I. 0–6.2%), 5.8% (C.I. 0.6–11.0%), 5.4% (C.I. 0.6–10.1%), 5.3% (C.I. 0.5–10.1%) and 6.6% (C.I. 1.4–11.8%), respectively. The 5-year disease-free survival (DFS), and overall survival (OS) were 88% (C.I. 81–95%), and 91% (C.I. 84–97%), respectively. The only predictor of worse 5-year pelvic control was stage (96.2% stage IA vs 87.7% for stage IB-II, p=0.043). ConclusionsIn stage I–II UPSC patients who predominantly receive adjuvant chemotherapy, IVRT as the sole form of adjuvant RT provides excellent locoregional control. The risk of isolated pelvic recurrence is too low to warrant routine use of external pelvic RT.

Why Do Pathological Stage IA Lung Adenocarcinomas Vary from Prognosis?: A Clinicopathologic Study of 176 Patients with Pathological Stage IA Lung Adenocarcinoma Based on the IASLC/ATS/ERS Classification

Patients with pathological stage IA adenocarcinoma (AC) have a variable prognosis, even if treated in the same way. The postoperative treatment of pathological stage IA patients is also controversial. We identified 176 patients with pathological stage IA AC who had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China, between 2000 and 2006. No patient had preoperative treatment. The histologic subtypes of all patients were classified according to the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary lung AC classification. Patients' 5-year overall survival (OS) and 5-year disease-free survival (DFS) were calculated using Kaplan-Meier and Cox regression analyses. One hundred seventy-six patients with pathological stage IA AC had an 86.6% 5-year OS and 74.6% 5-year DFS. The 10 patients with micropapillary predominant subtype had the lowest 5-year DFS (40.0%).The 12 patients with solid predominant with mucin production subtype had the lowest 5-year OS (66.7%). Univariate and multivariate analysis showed that sex and prognositic groups of the IASLC/ATS/ERS histologic classification were significantly associated with 5-year DFS of pathological stage IA AC. Our study revealed that sex was an independent prognostic factor of pathological stage IA AC. The IASLC/ATS/ERS classification of lung AC identifies histologic categories with prognostic differences that could be helpful in clinical therapy.

Combination of Protein Coding and Noncoding Gene Expression as a Robust Prognostic Classifier in Stage I Lung Adenocarcinoma

Prognostic tests for patients with early-stage lung cancer may provide needed guidance on postoperative surveillance and therapeutic decisions. We used a novel strategy to develop and validate a prognostic classifier for early-stage lung cancer. Specifically, we focused on 42 genes with roles in lung cancer or cancer prognosis. Expression of these biologically relevant genes and their association with relapse-free survival (RFS) were evaluated using microarray data from 148 patients with stage I lung adenocarcinoma. Seven genes associated with RFS were further examined by quantitative reverse transcription PCR in 291 lung adenocarcinoma tissues from Japan, the United States, and Norway. Only BRCA1, HIF1A, DLC1, and XPO1 were each significantly associated with prognosis in the Japan and US/Norway cohorts. A Cox regression-based classifier was developed using these four genes on the Japan cohort and validated in stage I lung adenocarcinoma from the US/Norway cohort and three publicly available lung adenocarcinoma expression profiling datasets. The results suggest that the classifier is robust across ethnically and geographically diverse populations regardless of the technology used to measure gene expression. We evaluated the combination of the four-gene classifier with miRNA miR-21 (MIR21) expression and found that the combination improved associations with prognosis, which were significant in stratified analyses on stage IA and stage IB patients. Thus, the four coding gene classifier, alone or with miR-21 expression, may provide a clinically useful tool to identify high-risk patients and guide recommendations regarding adjuvant therapy and postoperative surveillance of patients with stage I lung adenocarcinoma.

Oncologic Outcomes of Laparoscopy-Assisted Distal Gastrectomy for Gastric Cancer

In both advanced and early gastric cancer with preoperatively suspected lymph node metastasis, extended lymph node dissection is needed to achieve R0. Since extended lymph node dissection is difficult to perform laparoscopically, few reports have reported long-term outcomes in large numbers of patients. The purpose of this study was to investigate oncologic outcomes after laparoscopy-assisted distal gastrectomy (LADG) with extended lymph node dissection. Between April 2004 and March 2010, LADG with extended lymph node dissection was performed at our hospital for 880 patients diagnosed with T1N0-1 or T2N0 (N is classified by Japanese topographic classification) gastric cancer in the lower or middle body of the stomach. D2 lymph node dissection was performed for stage IB (T1N1, T2N0) cancers. Modified D2 lymph node dissection was performed for stage IA (T1N0). Overall survival (OS), disease-free survival (DFS), and form of tumor recurrence at 4years were investigated retrospectively. Median follow-up was 42months. The 4-year OS was 98.2% for all patients. By stage, OS/DFS were 99.0/99.0% in stage IA patients, 95.9/95.9% in stage IB, 92.6/92.0% in stage IIA, and 90.0/92.9% in stage IIB. A total of 11 patients died, including 4 deaths from recurrence (liver metastasis, n=1; peritoneal dissemination, n=2; distant lymph node and bone metastases, n=1). There is 1 patient is alive with recurrence (liver). Mean time until recurrence was 14months. Oncologic outcomes were good in patients with T1N0-1 and T2N0 gastric cancer who underwent LADG with extended lymph node dissection. This approach appears effective for treating T1N0-1 and T2N0 gastric cancer.

The CXCL12-3′A allele plays a favourable role in patients with multiple myeloma

Multiple myeloma (MM) is a plasma cell malignancy characterized by bone marrow infiltration and the presence of a monoclonal protein in serum and/or urine. CXCR4 and its ligand CXCL12 are essential for neoplastic cell homing to bone marrow in haematological malignancies. The JAK2/STAT3 pathway, which is activated after CXCL12 binding to CXCR4, takes part in many signalling cascades which are linked to cell proliferation and cell survival. Constitutive activation of this pathway plays an important role in tumourigenesis and malignant transformation. The present study aimed to determine the association between the polymorphic features located within the CXCR4 (rs2228014) and CXCL12 (rs1801157) encoding genes and disease susceptibility and progression.For this purpose 172 individuals including 54 patients with MM and 118 healthy controls were typed for the CXCL12 (A/G) and CXCR4 (C/T) alleles using the PCR-RFLP technique.The CXCL12 alleles and genotypes segregated similarly among patients and controls while the CXCR4 T variant was less frequently represented among patients (OR=0.074, p<0.001). All patients with the CXCR4 T allele and 16 out of 48 with wild type genotype presented with grade III of MM according to the International Staging System (ISS) (p=0.047).The CXCL12-3′A variant was more frequently detected in patients with less advanced MM (9/17 vs. 7/38, p=0.012 for patients in stage IA or IIA vs. IIB, IIIA and IIIB, respectively). Moreover, patients lacking the CXCL12-3′A variant more frequently presented with ISS II-III (32/38 vs. 5/13, p=0.003 for patients lacking CXCL12-3′A with ISS>I vs. ISS=I).This favourable effect of the CXCL12-3′A allele was also seen in the analysis of patient survival (p<0.05). The impact of the CXCL12-3′A allele was confirmed by multivariate analyses.In conclusion, these results imply that the CXCL12-3′A allele plays a favourable role in patients with multiple myeloma.

Recurrence and survival outcomes following adjuvant therapy for early-stage uterine serous carcinoma (USC).

e16556 Background: The choice of adjuvant therapy for early-stage USC remains controversial. The objective of this study was to estimate the recurrence rates of patients with surgically resected early-stage USC stratified by observation alone or adjuvant therapy. Methods: A retrospective review of women with surgically-staged stage IA-II USC followed at M.D. Anderson Cancer Center between January 2000 and December 2011. Descriptive statistics were used to summarize the demographic and clinical characteristics of patients. We estimated the cumulative incidence of disease recurrence, overall survival (OS), and recurrence-free survival (RFS) as a function of adjuvant therapy received. Adjuvant therapy groups listed in the Table. Results: 80 patients included in study. 58 patients had stage IA, 14 had stage IB, and 8 had stage II disease. Mean age was 66.4 years. Median follow-up for all patients was 4.83 years (range: 0.02 – 18.16). Cumulative incidence of recurrence for the whole group was 0.18 (95% CI: 0.10 – 0.28) which was reached at 3.96 years and remained at this rate until rising to 0.23 (95% CI: 0.12 – 0.36) at 11.12 years. Adjuvant treatment was not significantly associated with decreased risk of recurrence (Table). RFS at 5 years for the whole population was 0.71 (95% CI: 0.59 – 0.80) and OS at 5 years was 0.76 (95% CI: 0.63 – 0.85). Adjuvant treatment was not significantly associated with RFS or OS. In a subset of stage IA patients, 4 of 27 patients in the observation or cuff alone group recurred compared with 1 of 16 patients in the chemotherapy +/- cuff group (HR 0.48, CI: 0.05 – 4.27, p=0.511). Conclusions: In this study, there were no observed differences between observation and adjuvant treatment modalities in recurrence rates or survival outcomes for patients with early-stage USC. The addition of adjuvant chemotherapy may reduce risk for recurrence in stage IA patients, but further study is needed. [Table: see text]

Detection of E2A-PBX1 fusion transcripts in human non-small-cell lung cancer

BackgroundE2A-PBX1 fusion gene caused by t(1;19)(q23;p13), has been well characterized in acute lymphoid leukemia (ALL). There is no report on E2A-PBX1 fusion transcripts in non-small-cell lung cancer (NSCLC).MethodsWe used polymerase chain reaction (PCR) to detect E2A-PBX1 fusion transcripts in human NSCLC tissue specimens and cell lines. We analyzed correlation of E2A-PBX1 fusion transcripts with clinical outcomes in 76 patients with adenocarcinoma in situ (AIS) and other subgroups. We compared mutation status of k-ras, p53 and EGFR in 22 patients with E2A-PBX1 fusion transcripts.ResultsWe detected E2A-PBX1 transcripts in 23 of 184 (12.5%) NSCLC tissue specimens and 3 of 13 (23.1%) NSCLC cell lines. Presence of E2A-PBX1 fusion transcripts correlated with smoking status in female patients (P = 0.048), AIS histology (P = 0.006) and tumor size (P = 0.026). The overall survival was associated with gender among AIS patients (P = 0.0378) and AIS patients without E2A-PBX1 fusion transcripts (P = 0.0345), but not among AIS patients with E2A-PBX1 fusion transcripts (P = 0.6401). The overall survival was also associated with status of E2A-PBX1 fusion transcripts among AIS stage IA patients (P = 0.0363) and AIS stage IA female patients (P = 0.0174). In addition, among the 22 patients with E2A-PBX1 fusion transcripts, 12 (54.5%) patients including all four non-smokers, showed no common mutations in k-ras, p53 and EGFR.ConclusionsE2A-PBX1 fusion gene caused by t(1;19)(q23;p13) may be a common genetic change in AIS and a survival determinant for female AIS patients at early stage.