Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma

To identify genetic mechanisms controlling bone marrow microcirculation and angiogenesis in patients with plasma cell disease we simultaneously performed bone marrow dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and cytogenetics (iFISH) on CD138 purified plasma cells of MGUS (n=31) and untreated multiple myeloma (MM) (n = 87) patients. The adverse cytogenetic abnormalities gain of 1q21, deletion 17p13 and deletion 13q14 significantly correlated with at least one DCE-MRI finding (aberrant "focal" microcirculation pattern, increase in median microcirculation parameter Amplitude A or exchange rate constant kep). We conclude that gain of 1q21, deletion 13q14 and deletion 17p13 trigger the angiogenic cascade in MM. Our findings will have important implications for the design, analysis and stratification for clinical studies of patients with MM in particular if compounds with antiangiogenic activity are used.     

Nonsecretory and Light Chain Escape in Patients With Multiple Myeloma

Background

Multiple myeloma (MM) is characterized by the secretion of monoclonal protein by malignant plasma cells in the vast majority of cases. We identified and analyzed patterns of disease relapse and progression associated with disappearance of the paraprotein (“nonsecretory [NS] escape”), or conversion from production of intact Ig molecule to its associated light chain (“LC escape”).

Effect of Routine Surveillance Imaging on the Outcomes of Patients With Classical Hodgkin Lymphoma After Autologous Hematopoietic Cell Transplantation

BackgroundPatients with relapsed and refractory classical Hodgkin lymphoma (cHL) are often treated with autologous hematopoietic cell transplantation (auto-HCT). After auto-HCT, most transplant centers implement routine surveillance imaging to monitor for disease relapse; however, there is limited evidence to support this practice.Patients and MethodsIn this multicenter, retrospective study, we identified cHL patients (n = 128) who received auto-HCT, achieved complete remission (CR) after transplantation, and then were followed with routine surveillance imaging. Of these, 29 (23%) relapsed after day 100 after auto-HCT. Relapse was detected clinically in 14 patients and with routine surveillance imaging in 15 patients.ResultsWhen clinically detected relapse was compared with to radiographically detected relapse respectively, the median overall survival (2084 days [range, 225-4161] vs. 2737 days [range, 172-2750]; P = .51), the median time to relapse (247 days [range, 141-3974] vs. 814 days [range, 96-1682]; P = .30) and the median postrelapse survival (674 days [range, 13-1883] vs. 1146 days [range, 4-2548]; P = .52) were not statistically different. In patients who never relapsed after auto-HCT, a median of 4 (range, 1-25) surveillance imaging studies were performed over a median follow-up period of 3.5 years.ConclusionA minority of patients with cHL who achieve CR after auto-HCT will ultimately relapse. Surveillance imaging detected approximately half of relapses; however, outcomes were similar for those whose relapse was detected using routine surveillance imaging versus detected clinically in between surveillance imaging studies. There appears to be limited utility for routine surveillance imaging in cHL patients who achieve CR after auto-HCT.     

Estimation of error in maximal intensity projection-based internal target volume of lung tumors: a simulation and comparison study using dynamic magnetic resonance imaging

PURPOSE: To evaluate the error in four-dimensional computed tomography (4D-CT) maximal intensity projection (MIP)-based lung tumor internal target volume determination using a simulation method based on dynamic magnetic resonance imaging (dMRI). METHODS AND MATERIALS: Eight healthy volunteers and six lung tumor patients underwent a 5-min MRI scan in the sagittal plane to acquire dynamic images of lung motion. A MATLAB program was written to generate re-sorted dMRI using 4D-CT acquisition methods (RedCAM) by segmenting and rebinning the MRI scans. The maximal intensity projection images were generated from RedCAM and dMRI, and the errors in the MIP-based internal target area (ITA) from RedCAM (epsilon), compared with those from dMRI, were determined and correlated with the subjects' respiratory variability (nu). RESULTS: Maximal intensity projection-based ITAs from RedCAM were comparatively smaller than those from dMRI in both phantom studies (epsilon = -21.64% +/- 8.23%) and lung tumor patient studies (epsilon = -20.31% +/- 11.36%). The errors in MIP-based ITA from RedCAM correlated linearly (epsilon = -5.13nu - 6.71, r(2) = 0.76) with the subjects' respiratory variability. CONCLUSIONS: Because of the low temporal resolution and retrospective re-sorting, 4D-CT might not accurately depict the excursion of a moving tumor. Using a 4D-CT MIP image to define the internal target volume might therefore cause underdosing and an increased risk of subsequent treatment failure. Patient-specific respiratory variability might also be a useful predictor of the 4D-CT-induced error in MIP-based internal target volume determination.     

Outcomes and patterns of failure in solitary plasmacytoma: a multicenter Rare Cancer Network study of 258 patients

PURPOSE: To assess the outcomes and patterns of failure in solitary plasmacytoma (SP). METHODS AND MATERIALS: The data from 258 patients with bone (n = 206) or extramedullary (n = 52) SP without evidence of multiple myeloma (MM) were collected. A histopathologic diagnosis was obtained for all patients. Most (n = 214) of the patients received radiotherapy (RT) alone; 34 received chemotherapy and RT, and 8 surgery alone. The median radiation dose was 40 Gy. The median follow-up was 56 months (range 7-245). RESULTS: The median time to MM development was 21 months (range 2-135), with a 5-year probability of 45%. The 5-year overall survival, disease-free survival, and local control rate was 74%, 50%, and 86%, respectively. On multivariate analyses, the favorable factors were younger age and tumor size <4 cm for survival; younger age, extramedullary localization, and RT for disease-free survival; and small tumor and RT for local control. Bone localization was the only predictor of MM development. No dose-response relationship was found for doses >30 Gy, even for larger tumors. CONCLUSION: Progression to MM remains the main problem. Patients with extramedullary SP had the best outcomes, especially when treated with moderate-dose RT. Chemotherapy and/or novel therapies should be investigated for bone or bulky extramedullary SP.     

Significance of oligoclonal bands after stem cell transplantation in multiple myeloma cases

Objective: To determine the characteristics of oligoclonal bands that are frequently detected by serum proteinelectrophoresis (SPEP) and immunofixation electrophoresis (IFE) after stem cell transplantation. Methods: Weretrospectively analyzed 56 patients with multiple myeloma (MM) undergoing transplantation, and standardimmunofixation electrophoresis was used to identify and quantify paraproteins. Results: The median follow-upwas 35 months (range, 10-76months) and 21 patients relapsed. Twelve (25.0%) demonstrated oligoclonal bandsafter a median time 1.4 months (range, 1-3months), with a median duration of 5.8 months (range, 1-15months).The majority patients with oligoclonal bands had normal quantities of immunoglobulins and the one year eventfree survival (EFS) was 92%, even higher than for patients without OBs (P=0.002). Conclusion: Oligoclonalbands frequent develop post-transplantation in MM cases. In the vast majority of patients, they may notrepresent relapsed disease, and more likely represent a transient phenomenon representing recovery of impairedimmunoglobulin production.     

淋巴增强因子1在多发性骨髓瘤中的表达及其临床意义

目的 探讨多发性骨髓瘤(MM)患者初诊及化疗后骨髓单个核细胞中淋巴增强因子1(LEF-1)mRNA表达及其临床意义.方法 应用实时荧光定量聚合酶链反应(RFQ-PCR)测定42例MM初诊患者LEF-1 mRNA表达水平.并以20例明确血液系统非恶性疾病患者为对照组.结果 初诊MM患者LEF-1 mRNA中位表达水平高于对照组[0.01068(0.00017~0.14100)比0.00101(0.00009~0.00233)],差异有统计学意义(U=91.00,P<0.001);MM患者化疗后LEF-1 mRNA中位表达水平较化疗前下降[0.00011(0.00001~0.01548)比0.01068(0.00017~0.14100)],差异有统计学意义(U=343.0,P<0.001);化疗后MM疾病进展(PD)组患者LEF-1 mRNA中位表达水平高于非PD组[0.08386(0.00288~0.14100)比0.00345(0.00016~0.05660)],差异有统计学意义(U=343.0,P<0.001);初诊时LEF-1 mRNA表达水平相对较高的MM患者2年总生存(OS)率更低[高表达组为47.6%,低表达组为65.5%],差异有统计学意义(χ2=3.931,P=0.0414).结论 LEF-1可能参与MM的发生、发展,LEF-1水平可能是评估MM患者预后不良及PD指标,且其可能成为有效治疗MM的新靶点.     

Detection of malignant bone marrow involvement with dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: The purpose of this study was to evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (dMRI) in detecting bone marrow involvement in cancer patients. PATIENTS AND METHODS: We studied 50 consecutive patients with histologically confirmed malignant dissemination to the bone marrow, using dMRI of the lumbosacral spine. Time-signal intensity curves were generated from regions of interest (ROIs) obtained from areas of obvious bone marrow disease (group B). In 16 patients from group B with focal disease, ROIs were also placed on areas with apparently normal bone marrow on static magnetic resonance images (group C). Twenty-two patients with no history of malignancy were used as a control group (group A). Wash-in (WIN) and wash-out (WOUT) rates, time to peak (TTPK), time to maximum slope (TMSP) values and WIN/TMSP ratios were calculated for each patient. Mean values for the three groups were compared statistically. Six patients from group B had follow-up dMRI after chemotherapy: four patients achieved a clinical partial response and two had resistant disease. RESULTS: A significant difference was found between groups A and B for all values. Between groups A and C, in spite of the similar static MRI appearance, all values were significantly different. Between groups B and C, a significant difference was found for WIN, WOUT rates and WIN/TMSP ratio. Follow-up dMRI data analysis correlated well with clinical staging. CONCLUSIONS: dMRI can distinguish normal from malignant bone marrow. It may identify malignant bone marrow infiltration in patients with negative static MRI and serve as both a diagnostic and prognostic tool for patients with bone marrow malignancies.     

Phase II study of teniposide (VM-26) in multiple myeloma

From September 1979 to December 1983, a phase II trial with teniposide (VM-26) in multiple myeloma (MM) was conducted at our institution. Of the 30 patients entered, 25 were evaluable for response, 12 previously treated with M-2 protocol and 13 previously untreated elderly (greater than or equal to 70 years) patients. A median of nine cycles (range 1-21) of VM-26 was administered. Seven responses (28%) according to Myeloma Task Force criteria were observed with a median duration of 4 months (range 2-12+). Four responses (33%) were observed in the 12 previously treated patients. Overall toxicity was mild. VM-26 seems an active drug in MM, without significant toxicity even in elderly patients.     

The kinetics of the visible growth of a primary melanoma reflects the tumor aggressiveness and is an independent prognostic marker: a prospective study

Primary melanoma (MM) could be a good model to test an intuitive concept: a cancer that is growing fast in its early phase is likely to have a high aggressiveness. Since MMs are visible tumors, many patients can provide information to indirectly assess the kinetics of their lesion. A prospective study was designed to assess if the kinetics of the visible growth of a primary MM, as described by the patient, could be a noninvasive prognostic marker. The ratio of MM thickness to delay between MM appearance and MM removal was used as a surrogate value for the kinetics of the MM growth. To assess the delay between MM appearance and removal, 362 patients with self-detected invasive MM fulfilled a detailed questionnaire, which provided 2 types of estimations of this delay and thus 2 melanoma kinetics indexes (MKI and MKI*). After a median follow-up of 4 years, univariate and multivariate analyses assessed whether relapse-free survival was linked to MKI or MKI*. MKI was significantly predictive of relapse-free survival (HR = 1.84 [1.51-2.25]) and relapse at 1 year (RR = 2.93 [1.84-4.69]), independently from Breslow thickness. MKI was retained in multivariate prognostic models, just after thickness and before other usual markers. MKI* was also a significant independent risk marker, although less predictive. In this model, the initial growth kinetics of a cancer reflects its aggressiveness and a high index predicts a short-term relapse. The "subjective" data obtained from patients about their MM history, although usually neglected, can thus provide a better prognostic marker than many "objective" tests.     

Ovarian sex cord-stromal tumors in children and adolescents.

PURPOSE: To develop diagnostic standards and a risk-adapted therapeutic strategy for ovarian sex cord-stromal tumors (OSCST). PATIENTS AND METHODS: Fifty-four patients were prospectively enrolled as follow-up patients onto the German Maligne Keimzelltumoren protocols. Surgical protocols and histopathology were reviewed centrally (53 patients with complete data). Surgery included ovariectomy in 18 patients, salpingo-ovariectomy in 34 patients, and hysterectomy in one patient. Patients with stage IA tumors were followed-up at regular intervals, whereas nine patients with stage IC and six patients with stage II to III tumors were treated with cisplatin-based chemotherapy. RESULTS: International Federation of Gynecology and Obstetrics stage was IA in 27 patients, IC in 21 patients, II in three patients, and III in three patients. After a median follow-up of 59 months (range, 6 to 193 months), event-free survival +/- SD was 0.86 +/- 0.05 (47 of 54 patients) and overall survival was 0.89 +/- 0.05 (49 of 54 patients). Prognosis correlated with stage (event-free survival +/- SD: IA, 1.0 [27 of 27 patients]; IC, 0.76 +/- 0.09 [16 of 21 patients]; and II/III, 0.67 +/- 0.19 [four of six patients]; P =.02). Ten of 15 patients treated with chemotherapy, including four of six stage II to III patients, are alive after a median follow-up of 33 months. CONCLUSION: On the basis of a standardized clinical and histopathologic assessment, risk-adapted therapeutic strategies for OSCST can be evaluated. Considering our experience, we would recommend that stage IA tumors be followed up at regular intervals, whereas we would recommend cisplatin-based chemotherapy in stage IC tumors with preoperative rupture or malignant ascites, especially those with high mitotic activity. Finally, cisplatin-based chemotherapy also seems to be effective in advanced-stage tumors.     

Second primary tumors in patients with cutaneous malignant melanoma

BACKGROUND: Several studies report coexistent or subsequent primary tumors (SPT) among patients with malignant melanoma (MM), with the rate of incidence ranging from 1.5-20% depending on the sample size and the length and completeness of follow-up. METHODS: The authors followed a cohort of patients with cutaneous MM who were diagnosed and treated at the City of Hope National Medical Center to determine the incidence rate of SPT and associated risk factors. Five hundred eighty-five patients (median age at diagnosis, 43 years) were diagnosed and treated for MM between 1952 and 1996 and followed for a median of 6.5 years (range, 0.0-37.0 years). Ninety-six percent of the cohort had been treated by surgery alone. RESULTS: Thirty-seven patients developed an SPT. These included skin cancers (n = 23), carcinoma of the urinary bladder, breast carcinoma, and lymphoma (n = 3 each), lung carcinoma and prostate carcinoma (n = 2 each), and cervical carcinoma (n = 1). The estimated cumulative rate of incidence after MM was 5% at 5 years for any SPT, 3.7% for a second skin cancer, and 1.1% for a second solid tumor. Overall, the current cohort of MM patients was found to be at an increased risk for developing a subsequent melanoma (standardized incidence ratio [SIR], 4.5; 95% confidence interval [95% CI], 1.2-10.0) when compared with the general population. Older men (age > 50 years at the time of diagnosis of MM) were at an increased risk of developing subsequent bladder carcinoma (SIR, 6.4; 95% CI, 1.2-15.7). CONCLUSIONS: Patients diagnosed with MM are at an increased risk of developing subsequent MM and bladder carcinoma. Issues to be addressed in future studies include interactions between environmental exposures and genetic susceptibility and the identification of individuals at increased risk.     

Clinicopathological Features of Patients with Malignant Mesothelioma in a Multicenter,Case-Control Study: No Role for ABO-Rh Blood Groups

Background: Malignant mesothelioma (MM) is an aggressive tumor of mesothelial surfaces. Previous studieshave observed an association between ABO blood groups and risk of certain malignancies, including pancreaticand gastric cancer; however, no information on any association with MM risk is available. The aim of this studywas to investigate possible associations amoong MM clinicopathological features and ABO blood groups and Rhfactor. Materials and Methods: In 252 patients with MM, the ABO blood group and Rh factor were examined andcompared with the control group of 3,022,883 healthy volunteer blood donors of Turkish Red Crescent between2004 and 2011. The relationship of blood groups with various clinicopathological features were also evaluatedin the patient group. Results: The median age was 55 (range: 27-86) and 61.5% of patients were male. While82.8% of patients had a history of exposure to asbestos, 60.7% of patients had a smoking history. Epithelioid(65.1%) was the most common histology and 18.7% of patients had mixed histology. Overall, the ABO bloodgroup distribution of the 252 patients with MM was comparable with the general population. The median overallsurvival (OS) was 14 months (95% confidence interval, 11.3-16.6 months). The median OS for A, B, AB, and Owere 11, 15, 16, and 15 months respectively (p=0.396). First line chemotherapy was administered to 118 patients.The median OS of patients on pemetrexed or gemcitabine was longer than patient who was not administeredchemotherapy [17 months (95%CI, 11.7-22.2) vs. 9 months (95%CI, 6.9-11.0); p<0.001]. Conclusions: The resultsof this study suggest that patients with MM can benefit from treatment with pemetrexed or gemcitabine incombination with cisplatin. We did not observe a statistically significant association between ABO blood groupand risk of MM.     

Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of an M.D. Anderson Cancer Center series

BACKGROUND: The goal of the current study was to assess the toxicity, safety, and efficacy of pentostatin in patients with T-cell lymphoid malignancies. METHODS: Patients were eligible if they had biopsy-proven T-cell lymphoma or leukemia and failure to respond to previous therapy or an expected complete response rate to conventional therapy of < 20%. Pentostatin was administered at an initial dose of 3.75 or 5.0 mg/m(2) by intravenous bolus daily over a consecutive 3-day period every 3 weeks. RESULTS: Forty-two of 44 patients enrolled in the study were evaluable. The median age of the patients was 62 years (range, 38-86 years). Patients received a median of 3 previous therapies (range, 0-10 previous therapies). Of these patients, 32 (76%) had mycosis fungoides/Sézary syndrome and 10 patients (24%) had other T-cell leukemias or lymphomas. The overall response rate was 54.8% (complete remission, 6 patients [14.3%]; partial remission, 17 patients [40.5%]). Durable responses were observed mainly in patients with Sézary syndrome or peripheral T-cell lymphoma. The median follow-up period for surviving patients was 20 months (range, 1-83+ months). The median duration of response was 4.3 months (range, 1-61 months). The most common toxicities were neutropenia, nausea, and CD4 suppression. A transient early "flare" of disease was observed in some responders. CONCLUSIONS: At these doses, pentostatin was reasonably well tolerated and is an effective drug for the treatment of T-cell lymphomas.     

Toxicity and activity of docetaxel in anthracycline-pretreated breast cancer patients: a phase II study

Docetaxel has proven effective in advanced breast cancer. Myelosuppression and cumulative fluid retention syndrome are troublesome, potentially avoidable toxicities. In this consecutive cohort study, docetaxel (100 mg/m2 by 1 hour i.v. infusion, q3 weeks) activity and toxicity was explored in 56 anthracycline-pretreated patients (eligible: 55: median age: 51 years [range: 28-68 years]; median performance status: 0 [range: 0-3]) with metastatic breast cancer, using two different granulocyte colony-stimulating factor and steroid pre- and postmedication schedules. Twenty-nine patients (group A) received a 5-day oral prednisone premedication, and 26 (group B) received 4-day low-dose i.m. dexamethasone; group B patients also received prophylactic granulocyte colony-stimulating factor. All patients were evaluable for toxicity and 53 for response. Prophylactic granulocyte colony-stimulating factor significantly lowered the incidence of grade III-IV neutropenia and neutropenic fever (p = 0.0001 and 0.01, respectively). The incidence of moderate-severe fluid retention syndrome was lower in patients receiving i.m. dexamethasone (p = 0.08). Overall response rate was 53% (4 complete responses/24 partial responses, 95% confidence interval 39.4-66.2%); 32% have stable disease and 15% progressive disease. In 21 anthracycline-refractory/resistant patients, as well as in 10 paclitaxel-pretreated patients, the overall response rate was 50%. Docetaxel is highly active in anthracycline- and paclitaxel-pretreated metastatic breast cancer, with manageable toxicity. Optimal use of both granulocyte colony-stimulating factor support and steroid premedication deserves further investigation.     

Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: who benefits?

BACKGROUND: This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression-free interval > or = 3 months. METHODS: One hundred seventeen patients with relapsed EOC after a clinical complete remission duration > or = 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using log-rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model. RESULTS: The median patient age at the time of relapse was 53 years (range, 20-78 years). The median survival was 22 months and the estimated 5-year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to > or = 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured < or = 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. < or = 1 cm [P = 0.1211], < or = 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1-2 cycles vs. 3-5 cycles [P = 0.0144]; 1-2 cycles vs. > or = 6 cycles [P < 0.0001]; and 3-5 cycles vs. > or = 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106). CONCLUSIONS: SCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted > or = 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy.     

RB1 mutations and second primary malignancies after hereditary retinoblastoma

Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199 survivors of hereditary retinoblastoma with a documented RB1 germline mutation diagnosed between 1905 and 2005. In total, 44 hereditary retinoblastoma survivors developed a second primary malignancy after a median follow-up of 30.2 years (range 1.33-76.0). A significantly increased risk of second primary malignancy was observed among carriers of one of the 11 recurrent CGA>TGA nonsense RB1 mutations (hazard ratio (HR) = 3.53; [95% confidence interval (CI) = 1.82-6.84]; P = .000), and there was a significantly lower risk for subjects with a low penetrance mutation (HR = .19; [95% CI = .05-.81]; P = .025). Our findings suggest a genotype-phenotype correlation for second primary cancers of retinoblastoma survivors and may impact on long-term surveillance protocols of patients with hereditary retinoblastoma, if confirmed by future studies.     

Evaluation of prognostic significance of Revised International Staging System in multiple myeloma北大核心CSCD

Objective: To analyze the influence of Revised International Staging System (RISS) on the prognosis and treatment of multiple myeloma (MM). Methods: The clinical information of two hundred and fifty-nine newly diagnosed patients with MM was retrospectively analyzed. The survival and prognosis of these MM patients was compared by using Durie-Salmon (DS) staging, International Staging System (ISS) and RISS, respectively. The influence of use of bortezomib and autologous stem cell transplantation (ASCT) on the prognosis of patients with MM according to RISS was evaluated. Results: The median age of 259 patients with MM was 58 years (range: 34-87 years). The ratio of male to female was 1.3: 1. The median follow-up time was 32 months (range: 1-188 months), and the median progression-free survival (PFS) and median survival time were 45 and 67 months, respectively. In 239 patients with MM according to DS staging, the patients with DS stage I, II and III MM were accounted for 4.2%, 16.7% and 79.1%, respectively; the median PFS were 68, 41 and 44 months, respectively (P = 0.496), and the median survival time were 99, 64 and 67 months (P = 0.478); the 5-year PFS rates were 60.0%, 38.1% and 31.3% (P = 0.208), and the 5-year overall survival (OS) rates were 60.0%, 60.9% and 53% (P = 0.533). In 236 patients with MM according to ISS, the patients with ISS stage I, II and III MM were accounted for 17.4%, 41.1% and 41.5%, respectively; the median PFS were 53, 48 and 38 months, respectively (P = 0.033), and the median survival time were 68, 92 and 57 months, respectively (P = 0.028); the 5-year PFS rates were 36.8%, 40.0% and 25.6% (P = 0.291), and the OS rates were 60.0%, 63.9% and 42.1%, respectively (P = 0.119). In 173 patients with MM according to RISS, the patients with RISS stage I, II and III MM were accounted for 9.2%, 81.6% and 9.2%, respectively; the median PFS were 68, 47 and 16 months (P = 0.022), and the median survival time were statistics not shown and 72 and 25 months, respectively (P = 0.001). The 5-year PFS rates were 55.6%, 34.7% and 11.1% (P = 0.049), and the OS rates were 80.0%, 59.2% and 22.2% (P = 0.012). The patients with RISS stage III MM had better prognosis in bortezomib-based combination chemotherapy group, and the median survival time was 30 months, which was longer than that of the routine chemotherapy group (14 months, P = 0.014). ASCT had significant difference neither in PFS nor in OS according to RISS (P > 0.05). Conclusion: The RISS is superior to DS staging and ISS in the prognostic significance. Patients with RISS stage III MM have poor prognosis, and the bortezomib can improve the prognosis. Copyright © 2018 by TUMOR. All rights reserved.     

Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma

Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 +/- 16.6 vs. 52.2 +/- 6.2 ng/mL [p < 0.001]; VEGF, 55.1 +/- 7.6 vs. 32.1 +/- 2.4 ng/mL [p < 0.001]; mean +/- SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r = 0.556, p < 0.001) and VEGF levels (r = 0.335, p < 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow-up at 42 months; median survival time, 9 vs. 20 months [log-rank, p = 0.017]; median time to progression, 5 vs. 10 months [log-rank, p = 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome.