Low-intermediate Risk Group Research Articles

The NCCN-IPI Helps to Identify Very High-Risk Patients with DLBCL and Can be Improved By Other Independent Clinical Factors Including Bulky Disease and beta2-Microglobulin

The International Prognostic Index (IPI) has been the basis for predicting the outcome of diffuse large B cell lymphoma (DLBCL). With the improvement in prognosis with immunochemotherapy the predictive power of the IPI has been questioned.Recently, the enhanced NCCN-IPI has been proposed to provide a better discrimination of risk groups. Additionally, other patient- and disease-specific factors not incorporated in the prognostic algorithms and easily assessed at diagnosis have been shown to impact on the clinical course. The prognostic value of the NCCN-IPI together with other clinical characteristics remains to be widely validated.We aimed to assess the power of NCCN-IPI in risk group discrimination and compare it with IPI, as well as to investigate if the Body Mass Index (BMI), gender, diameter of the largest mass and levels of β2-microglobulin have independent prognostic impact when controlling for NCCN-IPI risk.We conducted a retrospective analysis of consecutive R-CHOP treated de novo DLBCL cases diagnosed between January 2002 and December 2013 in a single center.Kaplan-Meier method was used to estimate the overall (OS) and progression-free survival (PFS) distributions for risk groups. Logrank test with p-value adjustment by Hochberg method was used for pairwise comparisons between risk groups within each index. Independent prognostic impact of BMI, gender, bulky disease and β2-microglobulin was assessed by multivariate analysis using Cox model.410 patients were included in the analysis, with a median age of 64 (16-89) years; 51% were male. The distribution according to age, stage, extranodal (EN) sites, performance status, β2-microglobulin, BMI and bulky disease (Table 1) were similar to published data.With a median follow-up of 59 months, 5-yr OS and PFS were 69% and 65%, respectively. The distribution of patients according to IPI and NCCN-IPI risk groups is detailed in Table 1. Both scores adequately stratified patients according to risk of progression and death. In our cohort OS and PFS of low and low-intermediate risk groups using the NCCN-IPI were not significantly different. We documented a migration of patients from low (62%) and high (48%) to intermediate risk groups using the NCCN-IPI compared to the IPI. This score allowed a better discrimination between high-intermediate and high-risk disease (pairwise comparison of OS and PFS within NCCN and IPI risk scores of p=0.0087 vs p=0.044 and p=0.032 vs p=0.096, respectively). Only 12 patients classified as intermediate-risk IPI migrated to high NCCN risk group. Of these, 5 relapsed and 6 died (4 of lymphoma).Multivariate analysis showed that bulky disease and β2-microglobulin are independent prognostic factors for OS and PFS when controlling for NCCN-IPI.Using a large series of unselected R-CHOP treated patients, we pursued the validation of the NCCN-IPI as a better prognostic tool for DLBCL. In contrast to the original series, the NCCN-IPI showed limited discrimination capacity for OS and PFS between low- and low-intermediate risk groups. However, the new prognostic index helps to identify particularly poor prognosis patients that might benefit from alternative therapies. We also identified bulky disease and β2-microglobulin as independent prognostic factors in addition to NCCN-IPI and that could be incorporated in future prognostic scores. Additional studies are needed to evaluate the ability of biomarkers to improve the clinical risk stratification systems. Table 1CharacteristicsValue, n (%)AgeMedian (range), yr64 (16-89)≥60 years241 (59%)Male208 (51%)Performance status (ECOG) ≥2a66 (16%)Stage ≥ III221 (54%)BMIbUnderweight (<18.5)15 (4%)Normal (18.5-24.9)170 (43%)Overweight (25.0-29.9)139 (35%)Obese (>29.9)73 (18%)Bulky disease (>7 cm)c157 (40%)β2 microglobulin >ULNd154 (45%)≥2 EN sites92(23%)BM, CNS, liver/GI or lung involvement136 (33%)IPIe vs NCCN-IPIe (%)Low12 vs 34Low-Int38 vs 26High-Int35 vs 20High18 vs 125-yr OS (%)IPI (low, low-int, high-int, high)87, 70, 59, 50p= 8x10-12NCCN-IPI (low, low-int, high-int, high)88, 82, 59, 47p= 2x10-125-yr PFS (%)IPI (low, low-int, high-int, high)86, 66, 51, 48p= 2x10-11NCCN-IPI (low, low-int, high-int, high)84, 78, 54, 45p= 7x10-10BM: bone marrow, CNS: central nervous system, GI: gastrointestinal, int: intermediate.a: 405 pts, b: 397 pts, c: 391 pts, d: 341 pts, e: 403 pts. DisclosuresNo relevant conflicts of interest to declare.

Early-Stage Endometrial Cancer: Recurrence Pattern and Survival Analysis from a Tertiary Cancer Centre in South India

The incidence of endometrial cancer is rising in India possibly due to the change in lifestyle and urbanization. Recent years have also shown a change in the adjuvant therapy for endometrial cancer. We evaluated the pattern of recurrence and survival of stage I and II carcinoma endometrium treated at our institution during a 5-year period. This was a single-institution retrospective analysis where all patients with early (Stage I and II) endometrial cancers treated from January 2004 to December 2008 were included. Data were retrieved from the hospital electronic medical records and hospital-based cancer registry. Details regarding the disease, initial treatment, follow-up, recurrence, and present status of the patient were collected. During the study period, 103 women with early endometrial cancer were identified. Patients were classified into low-risk, low-intermediate risk (LIR), high-intermediate risk (HIR), and high-risk (HR) groups according to the risk stratification used by the PORTEC study group. There were no recurrences in the low-risk group, whereas 9 % of LIR, 13.7 % of HIR, and 66 % of high-risk group recurred. The recurrence pattern was also distinctive between the groups with LIR having more vault recurrences, HIR and HR groups having distant recurrences. The local recurrences were salvageable whereas the distant recurrences were not. Overall and disease-free survival were 96.35 and 86.6 %, respectively. Endometrial carcinoma is mostly detected in early stages and has an excellent prognosis. Risk stratification is a prognostic indicator and also deciding factor in offering adjuvant therapy. Majority of uterus confined disease falls under intermediate risk group. Recurrences in LIR are locoregional and are salvageable with RT, while recurrences in HIR and HR are distant and not salvageable. EBRT with VBT improved DFS in both LIR and HIR groups when compared with no adjuvant treatment.

Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥ 7 cm); and 75.3% underwent ≥ 6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥ 6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

Can and should carotid ultrasound be used in cardiovascular risk assessment?: The internist's perspective

Cardiovascular risk management is a major and challenging task for internists. Risk scores using algorithms based on traditional risk factors are helpful in identifying patients in whom intensive prevention strategies are warranted. However there remains a need for more accurate screening tools to allow clinicians to individualize the primary prevention programs to their patients.Approximately 40–80% of apparently healthy, asymptomatic subjects exhibit increased thickness of the lamina intima-media of the carotid artery or have atherosclerotic carotid plaques. These abnormalities can be measured safely and at low cost by ultrasound. Subclinical carotid lesions are strongly associated with generalized atherosclerotic burden and the risk of future cardiovascular events. Although many cardiovascular risk management guidelines recommend the use of these parameters incorporation in clinical practice is still not commonplace.Based on the current literature it can be stated that in high risk patients there is no additional value of carotid ultrasound because even in the absence of carotid lesions these patients should receive an intensive risk reduction regime. In the large low-intermediate risk group however carotid ultrasound findings carry subtle but possibly clinically relevant information about cardiovascular risk profile. The effect of treatment decisions based on carotid ultrasound parameters has not been studied. Sequential measurements to monitor progression and evaluate treatment response on an individual basis are not sufficiently reproducible.We therefore recommend the use of carotid ultrasound in low to intermediate risk patients but emphasize the importance of interpreting the results in conjunction with all cardiovascular risk factors and avoid follow-up measurements.

A Novel and Significant Predictor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: The Prognostic Nutritional Index (PNI)

Background: Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis. The prognostic nutritional index (PNI) is reported to be associated with survival in several types of tumors. The prognostic value of PNI in lymphoma remains unclear. The aim of the present study is to evaluate the prognostic significance of PNI in patients with ENKTL.Methods: 157 patients with newly diagnosed ENKTL were retrospectively evaluated between August 2000 and October 2011 at the Sun Yat-sen University Cancer Center. Patients in whom the combined albumin (g /l) +5x total lymphocyte count x 109/l ≥45 were allocated a PNI score of 0. Patients in whom this total was < 45 were allocated a score of 1.Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. The significance of differences between survival curves was tested using the log-rank test. Significant variables in the univariate analysis were considered variables for the multivariate survival analysis, which was performed using Cox regression mode.Results: Four-nine patients (31.2%) had an abnormal PNI (PNI=1). The characteristics of both groups are given in Table 1.After a median follow-up duration of 31.0 months, an estimated 5-year OS and PFS rate in 157 patients was 58.4% and 39.4%, respectively. Patients with pretreatment PNI score=1 had lower complete remission rates (P= 0.018) and worse OS (5-year OS: 71.7% vs 21.8.0%,P<0.001) and PFS (P<0.001) compared with PNI score=0 patients. The survival curves according to PNI are shown in Fig. 1.Using the International Prognostic Index (IPI) and peripheral T-cell lymphoma (PIT) scoring systems, more than 70% of all cases were in the low-risk category (with no or one adverse factor), but these two prognostic models failed to differentiate between patients with different outcomes in the low-risk group. PNI could differentiate low-risk patients using IPI and PIT scoring (all P< 0.05).The Korean Prognostic Index (KPI) model balanced distribution of patients into different risk groups better than the IPI and PIT models. However, the KPI model also failed to significantly differentiate between patients with different outcomes in low and low intermediate risk group (P=0.859). PNI also helped to differentiate between patients with different prognosis in low and low intermediate risk group (P=0.000).However, the KPI prognostic model failed to show significant prognostic value among patients with PNI=0 (P=0.646) or among the patients with PNI=1 (P=0.115). The survival curves according to KPI and PNI are shown in Fig. 2.Conclusions: PNI is an independent predictor of survival in ENKTL and is superior to IPI, PIT and KPI.Table 1Baseline Characteristics of Patients by PNI LevelCharacteristicsPNI score =0PNI score =1P10849Age (median [range], yr)42(9-77)45(12-76)0.031<6096(88.9)37(75.5)>6012(11.1)12(24.5)Gender0.444Female33(30.6)18(36.7)Male75(69.4)31(63.3)ECOG PS<0.0010-1107(99.1)40(81.6)2-31(0.9)9(18.4)B symptoms (yes)45(41.7)36(73.5)<0.001LDH >245 U/L19(17.6)29(59.2)<0.001Mass ≥5 cm12(11.1)6(12.2)0.836Extranodal sites ≥230(27.8)27(55.1)0.001Regional LN involvement60(55.6)40(81.6)0.002Bone marrow involvement0(0.0)3(6.1)0.009Primary sites0.006Nasal/nasopharynx area93(86.1)33(67.3)Extra-nasal/nasopharynx15(13.9)16(32.7)Ann Arbor stage0.001I/II93(86.1)31(63.3)III/IV15(13.9)18(36.7)IPI score<0.0010-191 (84.3)24(49.0%)2-517(15.7)25(51.0%)PIT score<0.0010-1106(98.1)36(73.5)2-42(1.9)13(26.5)KPI score<0.0010-169(63.9)9(18.4)2-439(36.1)40(81.6) [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Glasgow Prognostic Score (GPS) As a Significant Predictor of Diffuse Large B Cell Lymphoma Treated with the R-CHOP in China

Background: The Glasgow Prognostic Score (GPS), consisting of C-reactive protein (CRP) and albumin (Alb), is clinically useful for tumor behavior and shows significant prognostic value in several types of tumors. Several studies showed that GPS could be a predictive marker for advanced solid tumor, such as colorectal cancer, gastric cancer, etc. Now we performed a retrospective study to evaluate the relationship between GPS and prognosis of 160 patients with diffuse large B cell lymphoma (DLBCL) receiving R-CHOP chemotherapy between January 2001 and May 2010 at Shanghai Ruijin Hospital.Methods: Before treatment, the CRP and albumin were both tested for base line. Patients with both elevated CRP level (>10 mg/L) and hypoalbuminemia (<35 g/L) were given a score of 2. Patients with only one of these two biochemical abnormalities were allocated a score of 1. Patients in whom neither of these abnormalities was presented received a score of 0. We also identified International Prognostic Index (IPI) score of these patients.Results: Patients were assorted into three groups based on GPS at diagnosis. Survival curves were performed using the Kaplan-Meier method. Results showed that the overall survival (OS) and progress-free survival (PFS) rates for all patients were 78.1% and 68.1%, respectively. Analyzed by log-rank test, there was significant difference between GPS 1, GPS 2 and GPS 3 for OS (90.8% vs. 76.6% vs. 38.5%, p<0.001) and PFS (86.2% vs. 66.0% vs. 15.4%, p<0.001) (Fig 1a and b). In addition, the IPI, as a well-accepted prognostic system, though showed significant difference between lower risk group (IPI 0-2) and higher risk group (IPI 3–5) for OS (89.1% vs. 54.0%, p<0.01), failed to identify patients with poor prognosis in the lower risk group, since the low risk (IPI=0-1) and low-intermediate risk groups (IPI=2) appeared closely overlapping (p>0.05). While combining with the IPI model, GPS can have powerful prognostic value in the lower-risk (IPI=0-2) DLBCL patients, since patients with GPS score=0 had better OS (P<0.001) and PFS (P<0.001) than those with GPS score=1–2(Fig 2a and b).Conclusion: The GPS was a reliable and independent predictor of OS and PFS in patients with DLBCL treated with R-CHOP regimen. GPS combining with the IPI score may offer a more integrated prognostic system in the rituximab era of DLBCL. And inflammatory response might play an important role in the progression and survival of patients with DLBCL. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical Prognostic Models in Diffuse Large B-Cell Lymphoma Patients Are Still Essential in the Rituximab Era

Introduction: To evaluate a new enhanced IPI proposed by the National Comprehensive Cancer Network (NCCN-IPI) in DLBCL patients, we compared the international prognostic index (IPI), R-IPI and NCCN-IPI in DLBCL patients treated with rituximab, cyclophosphamide, hidroxydaunorubicin, vincristine and prednisone (R-CHOP).Methods: From June 2008 to November 2011 we retrospectively evaluated 146 DLBCL patients treated with R-CHOP-21 referred for cancer treatment in a single university institution in Brazil. Patient’s clinical data were assessed to calculate the IPI, R-IPI and NCCN-IPI.Results: Patient’s median age was 58.9 years (range 16 – 86); 85 (57.8%) were female. According to IPI, risk categories were low (n=41, 28.1%), low-intermediate (n=43, 29.5%), high-intermediate (n=37, 25.3%) and high (n=25, 17.1%). Using R-IPI, risk categories were very good (n=19, 13%), good (n=65, 44.5%) and poor (n=62, 42.5%). According to NCCN-IPI, risk categories were low (n=12, 8.2%), low-intermediate (n=52, 35.6%), high-intermediate (n=62, 42.5%) and high (n=20, 13.7%). At 30 months (median follow up 17.7 months - range 0.6-58.2 months) the overall survival (OS) was 75.5%. The progression-free survival (PFS) at a median follow-up of 16.3 months (range 0.6-52.4) was 68.3% for all patients. Using IPI, the OS at 30 months did not differ between low and low-intermediate risk patients (96.8% vs. 82.2%; p=0.136); however, it was higher than the OS of high-intermediate risk (n=37; 96.8% vs 74.1% p=0.11) and high-risk (n=25; 96.8% vs 41% p < 0.001) patients (Figure 1). The NCCN-IPI demonstrated significant differences in OS (p < 0,001) and PFS (p<0.001) among low-intermediate, high-intermediate, and high risk groups, with the high-risk group exhibiting worse OS (32.1% in 30 months) (Figure 2). According to IPI, the OS in high-risk patients was 41%. [Display omitted] [Display omitted] [Display omitted] Conclusion: In our study the NCCN-IPI, but not the IPI or R-IPI was able to discriminate a high-risk group of DLBCL patients treated with R-CHOP with worse OS. DisclosuresNo relevant conflicts of interest to declare.

Bone marrow biopsy in diffuse large B-cell lymphoma: Useful or redundant test?

Purpose. To determine the additional value of bone marrow biopsy (BMB) in the standard staging work-up of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), in terms of risk assessment and treatment planning.Material and methods. A total of 113 consecutive patients with newly diagnosed DLBCL who had undergone standard pretreatment evaluation, including serum lactate dehydrogenase measurement, Eastern Cooperative Oncology Group performance status assessment, computed tomography or 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography, and BMB, were retrospectively included. National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score and treatment strategy were determined in each patient, once without and once with taking into account BMB results. Numbers and percentages of BMB-induced changes on NCCN-IPI-based risk stratification (i.e. formation of low, low-intermediate, high-intermediate, and high risk groups) and choice of treatment were calculated, along with 95% confidence intervals (CIs).Results. BMB was positive in 18 of 113 patients (15.9%, 95% CI 10.2–23.9 %). BMB-induced changes on NCCI-IPI-based risk stratification occurred in 9 of 113 patients (8.0%, 95% CI 4.1–14.6%). Five patients were upstaged from low-intermediate to high-intermediate risk, and four patients were upstaged from high-intermediate to high risk. BMB findings changed treatment planning in none of the 113 patients (0.0%, 95% CI 0.0–4.0%).Conclusion. Although BMB results upstaged the NCCN-IPI-based risk stratification in a small number of cases, this did not have any therapeutic implications in our patient series. These findings support the omission of BMB from routine staging of newly diagnosed DLBCL in the current risk stratification and treatment era.

Stereotactic body radiotherapy as treatment for organ confined low- and intermediate-risk prostate carcinoma, a 7-year study.

Objectives: Stereotactic body radiation therapy (SBRT) takes advantage of the prostate’s low α/β ratio to deliver a large radiation dose in few fractions. Initial studies on small groups of low-risk patients support SBRT’s potential for clinical efficacy while limiting treatment-related morbidity and maintained quality of life. This prospective study expands upon prior studies to further evaluate SBRT efficacy for a large patient population with organ confined, low- and intermediate-risk prostate cancer patients.Methods: Four hundred seventy-seven patients with prostate cancer received CyberKnife SBRT. The median age was 68.6 years and the median PSA was 5.3 ng/mL. Three hundred twenty-four patients were low-risk (PSA <10 ng/mL and Gleason <7), 153 were intermediate-risk (PSA 10–20 ng/mL or Gleason = 7). Androgen deprivation therapy was administered to 51 patients for up to 6 months. One hundred fifty-four patients received 35 Gy delivered in five daily fractions; the remaining patients received a total dose of 36.25 Gy in five daily fractions. Biochemical failure was assessed using the phoenix criterion.Results: Median follow-up was 72 months. The median PSA at 7 years was 0.11 ng/mL. Biochemical failures occurred for 11 low-risk patients (2 locally), 14 intermediate-risk patients (3 locally). The actuarial 7-year freedom from biochemical failure was 95.6 and 89.6% for low- and intermediate-risk groups, respectively (p < 0.012). Among patients with intermediate-risk disease, those considered to have low intermediate-risk (Gleason 6 with PSA >10, or Gleason 3 + 4 with PSA <10; n = 106) had a significantly higher bDFS than patients with high intermediate-risk (Gleason 3 + 4 with PSA 10–20 or Gleason 4 + 3; n = 47), with bDFS of 93.5 vs. 79.3%, respectively. For the low-risk and low intermediate-risk groups, there was no difference in median PSA nadir or biochemical disease control between doses of 35 and 36.25 Gy.Conclusion: CyberKnife SBRT produces excellent biochemical control rates. Median PSA levels compare favorably with other radiation modalities and strongly suggest durability of response. These results also strongly suggest that 35 Gy is as effective as 36.25 Gy for low- and intermediate-risk patients.

Joint serum tumor markers serve as survival predictive model of erlotinib in the treatment of recurrent non-small cell lung cancer

背景与目的分子靶向治疗是肺癌个体化治疗的方向，目前已有学者建立靶向治疗预测模型，为临床个体化治疗提供更多的指导。本研究探讨血清肺表面活性物质相关蛋白（pulmonary surfactant-associated protein D, SP-D）、转化生长因子-α（transforming growthfactor α, TGF-α）、基质金属蛋白-9（matrix metalloproteinase 9, MMP-9）、组织多肽特异性抗原（tissue polypeptide specific antigen, TPS）、肺腺癌相关抗原（Krebs von den Lungen-6, KL-6）与晚期复治非小细胞肺癌（non-small cell lung cancer, NSCLC）治疗疗效及生存的关系，并构建生存预测模型。方法采用酶联免疫吸附法（enzyme-linked immuno sorbent assay, ELISA）检测114例晚期复治NSCLC患者治疗前外周血清中SP-D、TGF-α、MMP-9、TPS、KL-6含量，结合临床因素分析与厄洛替尼治疗疗效的关系，采用Kaplan-Meier生存曲线、Cox多因素生存分析模型进行单因素和多因素分析，并构建生存预测模型。结果114例患者厄洛替尼治疗总有效率为22.8%，稳定率为72.8%，中位无疾病进展时间（progression-free survival, PFS）为5.13个月，1年生存率为69.3%。SP-D > 110 ng/mL组的有效率及稳定率均高于≤110 ng/mL组（P=0.011, P=0.017），MMP-9≤535 ng/mL的稳定率高于 > 535 ng/mL组（P=0.009）。TPS < 80 U/L组的稳定率要高于≥80 U/L组（P=0.002）。SP-D > 110 ng/mL组的mPFS长于≤110 ng/mL组（5.95个月vs 3.25个月，P=0.009），MMP-9≤535 ng/mL的mPFS要长于 > 535 ng/mL组（5.83个月vs 3.47个月，P=0.046），KL-6中 < 500 U/mL组要优于≥500 U/mL组（6.03个月vs 3.40个月，P=0.040），TPS < 80 U/L组的mPFS要长于≥80 U/L组（6.15个月vs 2.42个月，P=0.014）。多因素分析显示吸烟史、EGFR基因野生型、末次化疗疗效进展、厄洛替尼治疗期间无皮疹、LDH升高和TPS≥80 U/L是PFS不佳的独立影响因素。通过建立预后预测模型，根据患者的预后指数可分成4组：低危组、中低危组、中危组和高危组，中位PFS分别是9.12个月、6.88个月、3.52个月和0.93个月，组间差异具有统计学意义（P < 0.001）。结论血清肿瘤标志物TPS水平联合患者临床特征建立预测厄洛替尼治疗晚期复治NSCLC生存模型，在临床上有一定的指导意义。

Standardized uptake value for 18F-fluorodeoxyglucose is correlated with a high International Prognostic Index and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma

The aim of this study was to evaluate whether the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose (FDG) correlates with the International Prognostic Index (IPI) and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma (DLBCL). Material and methods77 patients (age: 57.2±18.5, 40F, 37M) with DLBCL who underwent FDG PET/CT for initial staging were included. SUVmax of the predominant lesions were compared to Ann Arbor stage, IPI scores, the presence of extranodal involvement and the number extranodal sites. ResultsPET/CT detected nodal (n:25) and extranodal involvement (n:52) in all the patients. In 27 patients, extranodal disease could only be detected by PET. SUVmax of the predominant lesion in patients with extranodal disease was significantly higher than that of the patients who had only nodal disease (25±12 vs. 15.3±10 respectively, p=0.001). SUVmax significantly correlated with IPI scores; the average SUVmax was significantly correlated with the IPI: Mean SUVmax of the predominant lesion was 13.9±9.5 in patients with low risk (IPI=0–1), 14.2±8.8 in low-intermediate risk group (IPI=2) whereas 26.6±9.5 in high-intermediate risk group (IPI=3) and 25±13.6 in high risk group patients (IPI=4–5) (p=0.002). SUVmax was not correlated with clinical stage, the number of extranodal sites and serum LDH levels. ConclusionFDG uptake correlates with IPI and the presence of extranodal involvement in DLBCL. PET is a powerful method to detect extranodal disease in DLBCL. The correlation of SUVmax with these prognostic factors may highlight the importance of pretreatment FDG uptake as a metabolic marker of poor prognosis for patients with DLBCL.

Long Term Outcomes of Patients with Endometrial Carcinoma Treated with Radiation - Siriraj Hospital Experience

To evaluate treatment outcomes of patients with stage I-III endometrial cancer treated with postoperative radiation. A retrospective review of 166 endometrial cancer patients, undergoing surgery and postoperative radiotherapy at Siriraj Hospital from 2005-2008 was performed. Pathology was reviewed. Results of treatment were reported with 5-year loco-regional recurrence free survival (LRRFS), 5-year overall survival (OS), patterns of failure and toxicity, and according to stage and risk groups. Median follow up time was 62.8 months. Pathological changes were found in 36.3% of the patients after central reviews, leading to 19% changes in risk groups. Most of the patients (83.7%) received pelvic radiation (PRT) and vaginal brachytherapy (VBT). Five-year LRRFS and OS of all patients were 94.9% and 85.5%, respectively. There was no recurrence or death in low and low-intermediate risk groups. For the high-intermediate risk group, 5-year LRRFS and OS were 96.2% and 90.8%, respectively, and for the high risk group 90.5% and 71%. Late grade 3 and 5 gastrointestinal toxicity was found in 3% and 1.2% of patients, respectively. All of them received PRT 5,000 cGy in 25 fractions. Low and intermediate risk patients had good results with surgery and adjuvant radiation therapy. For high risk patients, postoperative radiation therapy alone appeared to be inadequate as the most common pattern of failure was distant metastasis.

The efficacy of EORTC risk tables in Japanese patients with non-muscle invasive bladder cancer.

331 Background: To predict recurrence and progression of non-muscle invasive bladder cancer (NMIBC), EORTC risk tables are widely used worldwide. EORTC risk tables were, however, developed on the basis of individual data from 2,596 NMIBC patients included in seven special European Organization for Research and Treatment of Cancer trials. Therefore, it is not clear the efficacy of these risk tables in clinical practice, especially in Japan. I will report the recurrence and progression rate on the basis of EORTC risk tables in Japanese NMIBC patients. Methods: A retrospective analysis of 619 patients with NMIBC treated between January 1998 and 2012 was performed. Patients were divided into three groups on the basis of EORTC risk tables. We compared recurrence- and progression-free survival rates between groups. Recurrence- and progression-free survival was estimated using the Kaplan-Meier method. Results: We evaluated the clinical outcome of 1,032 TUR-Bt. The recurrence rate is 32.3% in low risk group (n=31), 44.5% in intermediate risk group (n=757), and 49.4% in high risk group (n=85). The median recurrence free survival time is 87 months in low risk group, 35 months in intermediate risk group, and 25 months in high risk group. Although there are significant differences in recurrence free survival time between low risk group and intermediate risk group (p=0.0351), there are no significant differences between intermediate risk group and high risk group (p=0.1871). On the other hand, the progression rate is 1.6% in low risk group (n=128), 5.8% in intermediate risk group (n=451), and 18.0% in high risk group (n=294). The median progression free survival time is 176 months in low risk group, 131 months in intermediate risk group, and 109 months in high risk group. There are significant differences in progression free survival time between low risk group and intermediate risk group (p=0.0138), and between intermediate risk group and high risk group (p=&lt;0.0001). Conclusions: There is an urgent need to establish the standard of recurrence risk classification in Japan.

Standardized uptake value for 18F-fluorodeoxyglucose is correlated with a high International Prognostic Index and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma

The aim of this study was to evaluate whether the maximum standardized uptake value (SUVmax) of (18)F-fluorodeoxyglucose (FDG) correlates with the International Prognostic Index (IPI) and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma (DLBCL). 77 patients (age: 57.2±18.5, 40F, 37M) with DLBCL who underwent FDG PET/CT for initial staging were included. SUVmax of the predominant lesions were compared to Ann Arbor stage, IPI scores, the presence of extranodal involvement and the number extranodal sites. PET/CT detected nodal (n:25) and extranodal involvement (n:52) in all the patients. In 27 patients, extranodal disease could only be detected by PET. SUVmax of the predominant lesion in patients with extranodal disease was significantly higher than that of the patients who had only nodal disease (25±12 vs. 15.3±10 respectively, p=0.001). SUVmax significantly correlated with IPI scores; the average SUVmax was significantly correlated with the IPI: Mean SUVmax of the predominant lesion was 13.9±9.5 in patients with low risk (IPI=0-1), 14.2±8.8 in low-intermediate risk group (IPI=2) whereas 26.6±9.5 in high-intermediate risk group (IPI=3) and 25±13.6 in high risk group patients (IPI=4-5) (p=0.002). SUVmax was not correlated with clinical stage, the number of extranodal sites and serum LDH levels. FDG uptake correlates with IPI and the presence of extranodal involvement in DLBCL. PET is a powerful method to detect extranodal disease in DLBCL. The correlation of SUVmax with these prognostic factors may highlight the importance of pretreatment FDG uptake as a metabolic marker of poor prognosis for patients with DLBCL.

Risk Analysis of Early Implant Loss after Immediate Breast Reconstruction: A Review of 14,585 Patients

Early prosthesis loss is an infrequent but serious complication after breast reconstruction. We assessed perioperative risk factors associated with early device loss after immediate breast reconstruction (IBR) using the ACS-NSQIP datasets. We reviewed the 2005 to 2011 ACS-NSQIP databases identifying encounters for CPT codes 19357 and 19340. Patients were identified as experiencing a "loss of graft/prosthetic" based on a standard dataset variable. Patients who experienced a device loss were compared with those who did not with respect to perioperative characteristics. We identified 14,585 patients with an average age of 50.9 ± 10.6 years. A multivariate regression analysis determined that age (>55 years) (odds ratio [OR] 1.66, p = 0.013) (risk score = 1), class II obesity (OR 3.17, p < 0.001) (risk score = 3), class III obesity (OR 2.41, p = 0.014) (risk score = 3), active smoking (OR 2.95, p < 0.001) (risk score = 3), bilateral reconstruction (OR 1.67, p = 0.007) (risk score = 1), and direct-to-implant (DTI) reconstruction (OR 1.69, p = 0.024) (risk score = 1) were associated with early device loss. Odds ratios were used to assign weighted risk scores to each patient, and risk categories were broken into low risk (0 to 1, n = 9,349), intermediate risk (2 to 5, n = 5,001), and high risk (≥ 6, n = 233) groups. The risk of device loss was significantly higher with increased risk score (0.39% vs 1.48% vs 3.86%, p < 0.001). Early device loss following IBR is a complex multifactorial process related to identifiable preoperative risk factors. This study demonstrated that age, obesity, smoking, bilateral procedures, and DTI reconstructions are associated with increased risk of implant loss.

The clinic value of two-dimensional carotid strain in cardiovascular risk stratification

Objective To assess the two-dimensional carotid strain as an index of arterial stiffness in patients without carotid atherosclerotic plaques,and its clinic value in cardiovascular risk stratification.Methods All patients were divided into three groups (low risk,intermediate risk,high risk group) by Framingham cardiovascular risk scores,two-dimensional carotid circumferential strain (CS),carotid intimamedia thickness (IMT) were evaluated.CS was adjusted for pulse pressure (CS/PP).Results CS,CS/PP,IMT were significant difference between low risk and intermediate risk groups,low risk and high risk groups (P ＜0.05).IMT and CS were not significant difference between intermediate risk and high risk group (P =0.23,P =0.57).CS/PP was significant difference between three groups (P ＜0.05).Both CS and CS/PP were correlated with IMT (r =-0.30,r =-0.33,P ＜0.05).Conclusions Two dimensional strain could assess the carotid arterial mechanics.IMT and CS could evaluate the structural and functional alternations of carotid stiffness.Combining these two indices allowed more accurate evaluation of the subclinical phase of the atherosclerotic disease. Key words: Echocardiography; Carotid arteries; Atherosclerosis; Two-dimensional speckle tracking imaging

Prognostic Impact of High Hematogones in Acute Myeloid Leukemia

AbstractAbstract 1435▪▪This icon denotes a clinically relevant abstract Introduction:The response to AML treatment is very heterogeneous and relapse risk is high. Hematogones (HG) are B lymphoid cell precursors present in all individuals. HG absolute count grows after chemotherapy, during medullar recovery and it seems to be related to prognosis. Objectives:Determination of HG number in AML patients with intermediate-risk karyotype, with complete response (CR). Determine prognostic value for HG number in these patients. Methods:Retrospective analysis of 148 patients with non promyelocytic AML, treated with “7+3” chemotherapy induction, followed in our centre, from 1998 to 2011. HG quantification was executed after induction chemotherapy, with flow cytometry pannel (4 colours - CD34, CD10, CD19, CD20 e CD45) in blood marrow samples in patients with CR, according to Cheson et al. (JCO 2003). The patients characteristics were compared with a X2test for binary variables and a Mann-Whitney test for continuous variables. Survival was plotted with Kaplan-Meier curves and the data for the various groups were compared with a log-rank test. Multivariate analysis was performed with a Cox model after the proportional hazard assumption was checked. A p value less than 0.1 was considered to be statistically significant. Results:There were 124 patients achieving CR after induction chemotherapy “7+3”, with a median follow up of 32 months ([0–141]), 46,8% (n=58) were male, median age of 50 years ([17–66]). There were 91,1% (n=113) patients with de novo AML and 63,9% (n=76) with intermediate-risk karyotype. In this study 16,3% (n=20) went on transplantation. Relapse occurred in 53,2% (n=66), with a disease free survival (DFS) of 15 months ([0–140]). HG quantification was possible in 33,1% (n=41) of the patients. Applying a cutoff of 0.01% (Chantepie S et al. Blood 2011) we can find 31,7% (n=13) with HG>0.01%. These patients had better DFS, when comparing to patients with HG≤0.01% (median 16 vs 9 months, p=0,05), to equal overall survival.According to multivariate Cox model, the HG>0,01% is a independent predictive value for DFS (IC 95% [0,8533-54.259], p<0,07), when comparing to HG≤0,01%, age, leucocytosys (>20000/μL), karyotype-risk groups and WHO classification of AML. We established a good prognosis associated to HG>0,01% group: patients with HG≤0,01% have a 6.8 hazard ratio (HR) or relapse comparing with HG>0,01% group. Considering this information and applying it to karyotype-intermediate risk patients, it was possible to obtain two different groups with prognostic impact on the DFS: low intermediate risk (HG>0,01%) and high intermediate risk (HG<0,01%).The 3 year-DFS is 83,3% for low intermediate risk group and 50% for high intermediate risk patients (p<0,094). Conclusion:Using flow cytometry is a simple and reproductively method for detecting HG. This quantification in AML patients with CR has clinically relevance, with prognostic impact in DFS (16 vs 9 months, p=0,05). For HG levels superior to 0,01% after induction chemotherapy the risk of relapse is decreased. The HR associated to HG value allowed the stratification of the intermediate-risk group in two subgroups of patients (low intermediate risk group and high intermediate risk patients) with different DFS (83.3% vs 50% 3-y EFS, p<0,094). This subdivision can have implications on clinical decision for therapeutic strategy, in the heterogeneous intermediate-risk karyotype group. This cohort needs to be enhanced in order to validate this approach. Disclosures:No relevant conflicts of interest to declare.

Clinicopathologic Significance of CD11c, CD16 and FOXP3 Expression in Diffuse Large B-Cell Lymphoma (DLBCL) Patients Receiving Rituximab, Cyclophosphamide, Anthracycline, Vincristine, and Prednisolone (R-CHOP) Combination Chemotherapy

AbstractAbstract 5112 Backgrounds:The principal objective of this study was to determine whether the expressions of CD11c, CD16 and FOXP3 are predictive of clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients receiving treatment with rituximab, cyclophosphamide, anthracycline, vincristine, and prednisolone (R-CHOP) combination chemotherapy. Method:The study population consisted of 25 patients with DLBCL between January 2006 and December 2007. All the patients had been treated with R-CHOP combination chemotherapy. The R-CHOP regimen was as follows: 375 mg/m2 rituximab, 750 mg/m2 cyclophosphamide, 50 mg/m2 anthracycline, 1. 4 mg/m2vincristine were intravenously administered on day 1, and prednisolone 100 mg was medicated on days 1 to 5. This regimen was repeated every three weeks. The expressions of CD11c, CD16 and FOXP3 of primary tumors were immunohistochemically evaluated. Result:The mean age of the patients was 58 years (range, 27–77 years), and the pilot study population included 11 (44%) females and 14 (56%) males. The stages of the patients were I, II, III, and IV in 4 (16%), 5 (20%), 7 (28%), and 9 (36%), respectively. 60% of the patients were categorized as the low (44%) or low-intermediate risk group (16%) according to the International Prognostic Index (IPI). After a median follow-up of 57months, 8 patients (32%) developed disease recurrence or death. The estimated 5-year Progression free survival (PFS) and Overall survival (OS) were 65% (Figure 1) and 74% (Figure 2), respectively. 8 (32%), 18 (72%), and 17 (68%) were positive for CD11c, CD16 and FOXP3 expression, respectively. Univariate analysis of CD11c, CD16, FOXP3 for PFS and OS are shown in Figures 3–5. We noted no significant correlation between immunostaining of CD11c, CD16, FOXP3, and PFS. Patients with a CD11c -expressing DLBCL had a significantly higher 5-year OS rate than those without (p=0. 033, Figure 3). We classified patients according to the risk group. Each one counted for 1 point; In CD11c and FOXP3 stain, positive was counted as 0, negative was 1. In CD16, positive was counted as 1, negative was 0- and they were summed. The points were separated into low risk (0–1) and high risk (2–3) groups (Figure 6). We could found significant differences of PFS (p=0. 015) and OS (p=0. 046) between two groups. Conclusion:Even though this result was obtained from small number and retrospective data set, we can get a possibility of clinical significance of CD11c, CD16 and FOXP3 in DLBCL patients receiving R-CHOP therapy. Prospective large scale study is needed for confirming these promising our pilot study results. Disclosures:No relevant conflicts of interest to declare.

Clinical outcome of non-surgical treatment for primary small intestinal lymphoma diagnosed with double-balloon endoscopy

Primary small intestinal lymphoma (PSIL) is often treated with surgical resection, and therefore response to non-surgical treatment is rarely known. We retrospectively analyzed the clinicopathological features of 19 patients with PSIL, who had been diagnosed by double-balloon endoscopy (DBE) and had not received surgical treatment. The immunohistological phenotypes of 18 patients were B-cell lymphomas. Five patients had tumors within the jejunum, nine within the ileum and five in multiple sites including the duodenum. Most cases were in the low or low-intermediate risk group of the International Prognostic Index score. Seventeen patients received chemotherapy, with an overall response rate of 82.4%. The estimated overall survival at 5 years was 72.2%. Response to initial chemotherapy and levels of hemoglobin (Hb) and albumin (Alb) were identified as favorable prognostic indicators. We conclude that PSIL can be effectively diagnosed by DBE and shows a good prognosis with chemotherapy alone.

Further stratification of patients with multiple myeloma by International Staging System in combination with ratio of serum free κ to λ light chains

The serum free light chain (sFlc) levels were measured for 122 Chinese patients with newly diagnosed symptomatic multiple myeloma (NDSMM), and κ/λ ratios (rFlc) were calculated. The data were analyzed for the roles of sFlc and rFlc in the diagnosis and prognosis of MM. Abnormal sFlc and/or rFlc were detected in 99.2% of patients, demonstrating that the FLC assay is much more sensitive than the commonly used methods. Baseline sFlc and rFlc successfully predicted the overall survival (OS). The median OS was not reached (NR) versus 23 months for the low sFLC group (sFLC-κ 180 mg/L or sFLC-λ 592.5 mg/L) and high sFLC group (sFLC-κ ≥ 180 mg/L or sFLC-λ ≥ 592.5 mg/L) (p = 0.001), and NR versus 21 months for the low rFLC group (0.04 ≤ rFLC ≤ 25) and high rFLC group (p 0.001), respectively. Interestingly, the significant differences in OS between the low and high rFLC groups were not changed by bortezomib chemotherapy. In addition, patients were further stratified by three novel poor-prognosis factors (β2-microglobulin [β2-MG] 3.5 mg/L, albumin [ALB] 35 g/L, rFLC 25 or rFLC 0.04) that were developed from combination of the rFlc with the International Staging System (ISS): the low risk group (no factor), the low-intermediate risk group (one factor), the high-intermediate risk group (two factors) and the high risk group (three factors). The median OS for those groups was NR, NR, 24 months and 13 months, respectively (p 0.05). In conclusion, the sFLC assay was highly sensitive in the diagnosis of MM in Chinese patients. The prognostic potential of the ISS may be improved with the addition of rFLC.