Lower 5-year Overall Survival Research Articles

Which Patients with Isolated Para-aortic Lymph Node Metastasis Will Truly Benefit from Extended Lymph Node Dissection for Colon Cancer?

PurposeThe prognosis of patientswith colon cancer and para-aortic lymph node metastasis (PALNM) is poor. We analyzed the prognostic factors of extramesenteric lymphadenectomy for colon cancer patients with isolated PALNM.Materials and MethodsWe retrospectively reviewed 49 patients with PALNM who underwent curative resection between October 1988 and December 2009.ResultsIn univariate analyses, the 5-year overall survival (OS) and disease-free survival (DFS) rates were higher in patients with ≤ 7 positive para-aortic lymph node (PALN) (36.5% and 27.5%) than in those with > 7 PALN (14.3% and 14.3%; p=0.010 and p=0.027, respectively), and preoperative carcinoembryonic antigen (CEA) level > 5 was also correlated with a lower 5-year OS and DFS rate of 21.5% and 11.7% compared with those with CEA ≤ 5 (46.3% and 41.4%; p=0.122 and 0.039, respectively). Multivariate analysis found that the number of positive PALN (hazard ratio [HR], 3.291; 95% confidence interval [CI], 1.309 to 8.275; p=0.011) was an independent prognostic factor for OS and the number of positive PALN (HR, 2.484; 95% CI, 0.993 to 6.211; p=0.052) and preoperative CEA level (HR, 1.953; 95% CI, 0.940 to 4.057; p=0.073) were marginally independent prognostic factors for DFS. According to our prognostic model, the 5-year OS and DFS rate increased to 59.3% and 53.3%, respectively, in patients with ≤ 7 positive PALN and CEA level ≤ 5.ConclusionPALN dissection might be beneficial in carefully selected patients with a low CEA level and less extensive PALNM.

Adult prostatic sarcoma: A contemporary multicenter Rare Cancer Network study.

Adult prostatic sarcoma (PS) is a rare disease. While surgery is considered the standard approach, the role of other therapies is not completely established. We report results of the largest multicentric contemporary cohort of PS patients. This study included 61 adult PS patients treated in 16 American and European Institutions. Median age was 64.4 years (range: 22-87). Curative surgery was delivered in 48 patients (prostatectomy = 26, cystoprostatectomy = 22), usually with lymphadenectomy (n = 40). Curative radiotherapy (RT) was delivered in 32 patients, as radical (n = 5), neoadjuvant (n = 10), or postoperative treatment (n = 17). Eighteen patients received chemotherapy. None of the patients received hormonal therapy. Median follow-up was 72 months (95%CI: 55-not reached). Five-year local control (LC), overall survival (OS), cancer-specific survival, disease-free survival, and metastases-free rates were 47%, 53%, 56%, 35%, and 35%, respectively. Notably, curative RT (neoadjuvant, adjuvant, or definitive) was associated with improved 5-year LC (55% vs. 31%, P = 0.02) and OS (59% vs. 46%, P = 0.1). Surgically treated patients presenting with a cT3-4 tumor (n = 31), who received RT (n = 24), had a significantly improved 5-year LC (68% vs, 33%, P = 0.004) and OS (65% vs. 21%, P < 0.001) rates compared to patients not receiving RT. cT4 patients demonstrated a significantly lower 5-year OS (43% vs. 61%, P = 0.006) and LC (29% vs. 69%, P < 0.001) rates. Histologic subtype was not associated with LC and OS, but patients with prostatic stromal sarcoma, rhabdomyosarcoma, or sarcomatoid carcinoma had worse 5-year LC compared to other types (47% vs. 55%) and OS (49% vs. 58%). Adult PS has a poor prognosis. Locally advanced tumors have poor LC and OS rates. Curative RT should be considered part of the multidisciplinary approach to PS.

Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor

ABSTRACTObjective: Relapse is the major cause of treatment failure in acute lymphoblastic leukemia (ALL) of childhood; it is more frequent among high-risk patients from low-middle income than from high-income countries. The frequency, sites and outcome of relapsed ALL in children of northeast Mexico over a decade was documented.Methods: A retrospective analysis of 246 children belonging to a low-income group <16 years with de novo ALL during 2004–2015 was performed. Five-year overall survival (OS) and event-free survival was estimated by Kaplan–Meier analysis. Data on time, site, response to therapy and final outcome of relapse were analyzed. Hazard ratios (HRs) of relapse and death were estimated by the Cox regression model. Very early relapse was defined as that occurring in <18 months, early relapse between 18 and 36 months, and late relapse >36 months from diagnosis, respectively.Results: Eighty-seven (35.4%) children relapsed. Five-year OS was 82.6% in children without relapse vs. 42% for relapsed patients. Bone marrow (BM) was the most frequent site of relapse (51.72%). Isolated central nervous system (CNS) relapses occurred in 29.9%. Five-year OS was 11.2% for BM and 15.5% for early relapse. HR of relapse for organomegaly was 3.683, 2.247 for an initial white blood cell count >50 000 × 109/l and 1.169 for positive minimal residual disease status.Conclusion: A high rate of very early, CNS, and BM relapse with a considerably low 5-year OS requiring reassessment of therapy was documented. Organomegaly at diagnosis was a highly significant clinical predictor for relapse.

Prognostic role of primary tumor burden in extranodal nasal-type NK/T-cell lymphoma

Objective There is still a lack of effective clinical prognostic factors for predicting outcomes and guiding treatments in extranodal nasal-type NK/T-cell lymphoma (NKTCL). This study was aimed to investigate the clinical features and prognostic role of primary tumor burden (PTB). Methods A total of 1383 patients were recruited from ten hospitals, including 947 stage Ⅰ patients (68.5%), 326 stage Ⅱ patients (23.6%), and 110 stage Ⅲ-IV patients (8.0%). There were 751 patients (54.3%) presenting with high PTB (H-PTB). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was conducted for survival difference analysis. Meanwhile, a multivariate analysis was performed using the Cox regression model. Results H-PTB was associated with high invasive potential, high frequency of B symptoms, advanced stage, regional lymph node involvement, lactate dehydrogenase elevation, and poor performance status. The patients with H-PTB had significantly lower 5-year overall survival (OS) and progression-free survival (PFS) rates than those with low PTB (L-PTB)(OS: 50.2% vs. 72.1%, P=0.000; PFS: 41.8% vs. 62.5, P=0.000). PTB was an independent prognostic factor for both OS (HR=1.851) and PFS (HR=1.755) according to the Cox multivariate analysis. Moreover, H-PTB was associated with significantly lower locoregional control (LRC) in early-stage NKTCL, and the 5-year LRC rate was 71.6% in patients with H-PTB and 84.3% in those with L-PTB (P=0.000). Conclusions H-PTB is associated with multiple adverse clinical features in NKTCL, and it is an independent indicator for poor outcomes and LRC. H-PTB can be used as a reliable indicator for risk stratification and treatment decision. Key words: NK/T-cell lymphoma; Prognosis; Tumor burden

Role of radiotherapy in patients with stage I-II diffuse large B-cell lymphoma of waldeyer’s ring in remission after chemotherapy

Objective To investigate the impacts of adjuvant radiotherapy on the prognosis of patients with stage Ⅰ-Ⅱ diffuse large B cell lymphoma of Waldeyer’s ring (WR-DLBCL) who achieved complete remission (CR) after chemotherapy. Methods Clinical data were collected from 130 patients with stage Ⅰ-Ⅱ WR-DLBCL who were admitted to our hospital from 2005 and 2013. All the patients achieved CR after at least two cycles of cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone (CHOP)-based chemotherapy or rituximab plus CHOP (R-CHOP)-based chemotherapy. In the 130 patients, 43 received R-CHOP (including 25 patients undergoing radiotherapy) and 87 CHOP (including 76 patients undergoing radiotherapy); 29 received chemotherapy alone and 101 chemoradiotherapy. The survival rates were calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate prognostic analyses were made by the log-rank test and the Cox model, respectively. Results In all patients, the 5-year sample size was 101. The univariate analysis showed that patients with an Eastern Cooperative Oncology Group (ECOG) score of 0 had significantly higher 5-year overall survival (OS) and disease-free survival (DFS) rates than those with an ECOG score of 1(95.6% vs. 80.1%, P=0.000; 95.7% vs. 75.4%, P=0.029). Patients treated with chemotherapy alone had significantly lower 5-year OS and DFS rates than those treated with chemoradiotherapy (77.1% vs. 91.7%, P=0.048; 77% vs. 87.4%, P=0.037). The multivariate analysis by the Cox model showed that ECOG score was a prognostic factor for both OS and DFS (P=0.047, 0.003). Adjuvant radiotherapy was related to improved DFS rather than OS (P=0.039, 0.133). Conclusions Stage Ⅰ-Ⅱ WR-DLBCL patients with low ECOG scores have better prognosis than those with high ECOG scores. Patients with CR after chemotherapy may benefit from adjuvant radiotherapy. The conclusions need to be further confirmed by prospective randomized controlled trials. Key words: Diffuse large B cell lymphoma/chemotherapy; Diffuse large B cell lymphoma/radiotherapy; Prognosis

Survival Improvement in Therapy Related Myeloid Neosplasm ? a Single Center Analysis of 428 Patients

Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) arise after cytotoxic chemotherapy and/or radiotherapy administered for a prior neoplasm and have a dismal outcome (median survival of 8 months in the largest series published including 306 patients (pts), Smith, Blood 2003). Recent registry data suggested a continued increase in survival in AML (Derolf, Blood 2009) and we wondered whether this was also observed in the setting of t-AML/ MDS.All pts with a t-AML/MDS diagnosed and/or treated for their prior neoplasm at Gustave Roussy Cancer Center between July 1986 and 2016 were included in this retrospective study. Data regarding pts' demographics, primary diagnosis and treatment, latency time, cytogenetic, treatment and outcome were collected. The diagnosis of t-AML/MDS was based on the WHO 2016 classification. t-AML were classified based on cytogenetic results as favorable, intermediate and adverse according to international classification, t-MDS based on IPSS score as favorable (Low, Int-1) and adverse (Int-2 and High).428 pts were analyzed. The median age at diagnosis of t-AML/MDS was 56.4 years with a female predominance (60%). 224/428 (52.3%) pts had t-AML, 204/428 (47.7%) t-MDS. The most common primary malignancies were breast cancer (24%), non-Hodgkin lymphoma (15%), Hodgkin lymphoma (HL) (9%) and ovarian cancer (9%). Occurrence of t-AML/MDS following HL represented 26.6% of t-AML/MDS cases between 1986-96 comparing to 4 % between 2006-16 whereas breast cancer rose from 16% to 45%. Prior treatments included chemotherapy alone in 137/428 pts (32%), radiotherapy alone in 61 pts (14%) and both in 230 pts (54%).At diagnosis of t-AML/MDS, 295 pts (69%) were in complete remission (CR) of their prior neoplasm, 29 (7%) had a stable and 104 (24%) a progressive disease. Median interval between primary cancer and t-AML/MDS was 5 years (4.3 and 5.7 years for t-AML and t-MDS respectively, (p=0.03)). Furthermore, delay to develop t-AML/MDS after radiotherapy alone was longer compare to chemotherapy or both (6.1, 5.1 and 4.3 years, respectively (p=0.0087)). In the t-AML subgroup, 47% of pts presented unfavorable cytogenetic (including complex karyotype (20%) and 11q23 abnormalities (16.9%)), 26% intermediate and 26% favorable cytogenetic (core binding factor mutations (12.7%), t(15;17) (13.3%)). In the t-MDS subgroup, 78% of pts were considered adverse; complex karyotype, chromosome 7 and 5 abnormalities were found in 40.8%, 46.7% and 28.9% respectively. Pts received intensive chemotherapy (including 41 allografts), low dose chemotherapy (including 74 treatments with hypomethylating agents) and best supportive care in 42%, 24% and 34% respectively.The median overall survival (OS) was 10.6 months and the 5-year survival was 19.1% (Figure 1A). The 5-year OS of patients in CR of their prior neoplasm was 25.5% compared to 3.65 and 0% for pts with progressive and stable disease, respectively (p<0.001). 5-year OS was not statistically different between t-AML and t-MDS subgroups (23.3% vs 13.5%) and between hematologic or oncologic malignancies as primary diagnosis (12.6% vs 21.1%). Pts with favorable risk t-AML had better 5-year survival compared with patients with intermediate or unfavorable risk disease (55.5% vs 20% vs 12.1% respectively, p<0.001). In addition, favorable t-MDS was associated with better 5-year OS compared to adverse t-MDS (34.9% vs 6.6%, p<0.001). We next compared OS of pts diagnosed for their t-AML/MDS after or before July 2001. A trend for better OS for pts diagnosed in the last 15 years was observed (21.5% vs 15.1%, p=0.39). Interestingly outcome of t-AML patients with favorable subtype significantly improved over the last 15 years (68.8% vs 25%, p=0.03, Figure 1B) which was not the case for other cytogenetic subgroups and for t-MDS, especially pts with adverse prognosis (4.6% vs 3.9%, p=0.92). Pts who received allograft had a trend for better OS in the last 15 years (52.8% vs 21.5% p=0.2).t-AML/MDS are still associated with a low 5-year OS (19.1%) but our results are upper than previous publications. However, a significant improvement of survival in favorable t-AML was observed during the past 30-years, with a trend for pts who benefit from allograft. In addition to improve treatment for t-MDS pts, detection of the disease at the earliest stage is a real challenge to improve their survival. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis

The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined. To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging. Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014. Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5-year follow-up. One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five-year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004). An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging.

Body mass index as a prognostic factor in patients with extranodal natural killer/T-cell lymphoma, nasal type

Epidemiological evidence has shown that body mass index (BMI) can predict survival in several types of cancer. However, the role of BMI in extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is still unclear. This retrospective single-center study included 251 newly diagnosed patients to determine the prognostic value of BMI in ENKTL. Of these, 203 patients received chemoradiotherapy, 37 received chemotherapy alone, 8 received radiotherapy alone, and 3 received only best supportive care. With a median follow-up of 28 months, the estimated 3-year overall survival (OS) and progression-free survival (PFS) rates were 64.4% and 60.9%, respectively. The receiver-operating characteristic curve showed that 20.8 kg/m2 was the optimal cut-off of BMI to predict survival. BMI < 20.8 kg/m2 was associated with lower 3-year OS (52.8% vs. 72.9%, P = 0.001) and PFS (48.8% vs. 69.8%, P < 0.001) rates. Multivariate analysis indicated that BMI, performance status, lactate dehydrogenase (LDH) levels, chemotherapy, and radiotherapy were independent prognostic factors for OS. Furthermore, BMI, number of extranodal sites, performance status, LDH, and radiotherapy were predictive of PFS. These results suggest that BMI at the cut-off of 20.8 kg/m2 might be a prognostic factor in patients with ENKTL.

Survival Rates of Adults With Acute Lymphoblastic Leukemia in a Low-Income Population: A Decade of Experience at a Single Institution in Mexico.

The therapeutic progress for adults with acute lymphoblastic leukemia (ALL) has been slow, with a 5-year survival of 30% to 45% in developed countries. Scarce information is available regarding the treatment and survival rates from nonindustrialized populations. In the present study, the characteristics of adults with ALL at a single institution were documented. The clinical files of patients aged≥ 18 years who had been diagnosed with ALL from 2005 to 2015 at a reference center in Mexico were scrutinized. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method. The hazard ratios for death and relapse were estimated using Cox regression analysis. A total of 94 adults were included. Their median age was 33 years; 69 (73.4%) had high-risk and 25 (26.6%) had standard-risk ALL. Of the 94 patients, 67 (71.3%) achieved complete remission (CR), 20 (21.3%) experienced disease resistance, and 7 (7.4%) died early during induction to remission, mainly of sepsis. The 5-year EFS and OS was 23.4% and 31.1% for the whole group and 24.9% and 38.9% for patients who achieved CR, respectively. Of the 94 patients, 50 (43.9%) died of sepsis or disease progression. Relapse developed in 43 patients (45.7%). The median survival after relapse was 6.93 months. Bone marrow was the most frequent site of relapse (21 patients [48.8%]) and conferred a significantly lower 5-year OS of 16.4%. Adults with ALL in Mexico had high-risk characteristics and an increased relapse rate; however, the OS after CR was similar to the greatest achieved in developed countries, suggesting that a threshold for curing adult ALL with current therapeutic strategies has been reached.

Overexpression of cancer cell-derived immunoglobulin G correlates with poor prognosis in gastric cancer patients

Background: Various human epithelial origin cancers produce cytoplasmic immunoglobulin (Ig) G. Recent studies have elucidated that it was related with the tumorigenesis. This study was aimed to identify relationship between the cancer cell-derived IgG expression level and clinical parameters in gastric cancer (GC). Methods: Cancer cell-derived IgG expression was assessed using immunohistochemistry analysis in 231 primary GC tissues. The role of cancer cell-derived IgG on cell proliferation, migration and invasion were assessed. Results: Our results indicated that IgG was overexpressed in GC tissues (42.2%, 46/109) than in adjacent tissues (11.0%, 12/109, P vs. 37.2%, respectively). Upon univariate analysis, IgG positive group had significantly lower 5-year overall survival than the negative group (P=0.0361). Multivariate analysis showed IgG expression was an independent prognostic indicator for 5-year overall survival of patients with GC (P=0.018). Furthermore, knockdown of IgG by short interfering RNA (siRNA) resulted in reducing proliferation, migration and invasion of GC cell. Conclusions: Our results showed that cancer cell-derived IgG overexpression might be correlated with GC progression, and would be a novel biomarker to predict the prognosis of patients with GC.

Change in platelet count as a prognostic indicator for response to primary tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma.

To evaluate change in platelet count as an indicator of response to primary tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC). We conducted a multicentre retrospective analysis of patients with mRCC undergoing primary TKI therapy from May 2005 to August 2014. Change in platelet count was defined as post-treatment platelet count after the first cycle of treatment minus the pretreatment platelet count. Response Evaluation Criteria in Solid Tumours were used to define partial response (PR), stable disease (SD) and progressive disease (PD). Analysis was conducted between subgroups with stable/increased (+ΔPlt) and decreased (-ΔPlt) counts. The primary outcome was overall survival (OS), determined using Kaplan-Meier analysis. Multivariable analysis was conducted for risk factors associated with PD. A total of 115 patients with mRCC were analysed, of whom 19 (16.6%) had a +ΔPlt and 96 (83%) a -ΔPlt. More patients with a +ΔPlt had a Karnofsky score <80 (42.1 vs 14.6%; P = 0.005) and >2 metastatic sites (78.9 vs 51%; P = 0.041). More patients with +ΔPlt than with -ΔPlt had PD (89.4 vs 19.1%; P < 0.001) and more of those with -ΔPlt than with +ΔPlt had SD/PR (80.9 vs 10.6%; P < 0.001). Multivariable analysis showed that +ΔPlt (odds ratio [OR] 5.36, P < 0.001), Karnofsky score < 80 (OR 2.96, P = 0.002) and >2 metastatic sites at presentation (OR 1.87, P = 0.013) were risk factors for PD. Kaplan-Meier analysis showed a lower 5-year OS in patients with +ΔPlt than in those with -ΔPlt (23 vs 53%; P < 0.0001). +ΔPlt had a sensitivity of 48.6%, a specificity of 97.4%, a positive predictive value of 89.5% and a negative predictive value of 80.9% for PD. Patients with a -ΔPlt were more likely to respond to TKI therapy and had longer OS. +ΔPlt above baseline had a high specificity for PD after primary TKI. Further investigation is required to determine the utility of ΔPlt.

Primary site and regional lymph node involvement are independent prognostic factors for early-stage extranodal nasal-type natural killer/T cell lymphoma.

BackgroundNasal-type extranodal natural killer/T-cell lymphoma (ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract. However, it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement. The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL.MethodsTo develop a nomogram, we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index) and calibration curve.ResultsThe 5-year overall survival (OS) and progression-free survival (PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL (OS: 68.2% vs. 46.0%, P = 0.030; PFS: 53.4% vs. 26.6%, P = 0.010). The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage IIE ENKTCL (OS: 66.3% vs. 59.2%, P = 0.003; PFS: 51.4% vs. 40.3%, P = 0.009). Multivariate analysis showed that age >60 years, ECOG performance status score ≥2, elevated lactate dehydrogenase (LDH) level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year OS rate; age >60 years, elevated LDH level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year PFS rate. The nomogram included the primary site and regional lymph node involvement based on multivariate analysis. The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates, and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634, respectively.ConclusionsThe primary site and regional lymph node involvement are independent prognostic factors for early-stage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

Prognostic role of elevated preoperative systemic inflammatory markers in localized soft tissue sarcoma.

Systemic inflammation has been implicated in cancer development and progression. The aim of the present study was to evaluate whether pre-operative systemic inflammatory markers can predict outcomes in bone and soft tissue sarcomas. Relevant literature was mainly identified using Pubmed, EMBASE and CNKI. Patients' clinical characteristics, overall survival (OS), disease/relapse free survival (DFS/RFS) with high-level CRP or neutrophils to lymphocytes ratio (NLR) were extracted. The statistics extracted from Kaplan-Meier survival curves with log-rank p value were calculated with methods developed by Parmar, Williamson, and Tierney; multivariate Cox hazard regression analysis data were used directly in STATA 10.0. Pooled hazard ratio (HR) and 95% CI were calculated to evaluate the prognostic role of these systemic inflammatory markers (CRP/NLR). After full text review, 11 articles containing 1809 patients were identified as eligible articles. The meta-analysis for survival outcome showed significant prognostic value of systemic inflammatory markers including CRP and NLR in pre-operative blood. The combined HRs (95% CI) for five year overall survival (OS) and disease/recurrence free survival (DFS/RFS) were 2.54 [2.04, 3.16] and 2.28 [1.72, 3.04]. Specifically, higher NLR was associated with decreased 5-year OS (HR 3.75, 95% CI 1.24 to 11.37) and 3 year RFS/DFS (HR 2.43, 95% CI 0.84 to 7.05). Besides, the pooled HR showed a higher risk of 5-year disease progression (HR 2.55, 95% CI 1.60 to 4.08, I2 = 52%) and lower 5-year OS (HR 2.50, 95% CI 2.00 to 3.12, I2 = 0%) in sarcoma patients with high CRP level. We then grouped the meta-analysis by patient source (Asian and non-Asian), tumor stage (I/II or III/IV) and grade (high or low), respectively. All the subgroup analysis showed significant prognostic role in survival condition. The CRP/NLR levels are also found closely related with patient age, tumor stage and size. Higher level of pre-operative CRP and NLR demonstrated a significantly higher risk of recurrence and overall decreased survival rates in sarcomas.

The effect of postoperative morbidity on long-term survival after curative resection for extra-hepatic biliary tumors: A multi-institution analysis from the U.S. Extrahepatic Biliary Malignancy Consortium.

435 Background: Surgical resection is the cornerstone of curative therapy for extrahepatic biliary tumors (EHBTs) Postoperative complications (POCs) can negatively impact survival after oncologic resection. We evaluated the impact of POCs on survival after resection of EHBTs. Methods: We analyzed 914 patients from ten institutions of the U.S. Extrahepatic Biliary Malignancy Consortium who underwent curative resection for gallbladder adenocarcinoma (n=389), hilar (n=295) and distal (n=294) cholangiocarcinoma between 1998 and 2015. POCs were graded using the modified Clavien-Dindo system. Overall survival (OS) probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. Results: Median follow-up was 20 months. The median age was 66 years, and the overall complication rate was 54%. Complication rates were significantly higher in patients with distal or hilar cholangiocarcinoma (62%) when compared with gallbladder cancer (41%, p&lt;0.001). For all cancer types, patients who experienced POCs had lower 5-year OS when compared with those who did not (18% vs 28%, p&lt;0.001). On multivariate Cox regression, POC remained an independent predictor for decreased OS (HR 1.5, 95% CI 1.3-1.9, p&lt;0.001; Table). Among patients who experienced POCs, survival did not differ by greatest Clavien grade of complication experienced (p=0.89), however patients who had 2 or more POCs did have decreased long term survival when compared with patients with only a single POC (HR 1.5, 95% CI 1.2-1.8, p=0.001). Conclusions: POCs adversely affect long-term outcomes after curative resection for extra-hepatic biliary tumors. While any complication grade did not have a significant impact on long-term survival, increasing number of POCs did significantly worsen the prognosis for OS. [Table: see text]

Relationship of preoperative and postoperative myeloid-derived suppressor cells percentage with the prognosis in rectal cancer patients

To observe the change of myeloid-derived suppressor cells (MDSCs) percentage in peripheral blood after operation in rectal cancer patients and to examine its association with the prognosis. Blood samples of pre-operation and postoperative 21-day from 64 stage I(-III( rectal cancer patients who underwent surgery in Department of General Surgery, The Affiliated Cancer Hospital, Zhengzhou University between January and December 2009 were collected. MDSCs percentage was detected by flow cytometry. Its association with the prognosis of patients was analyzed. MDSCs percentage of postoperative 21-day decreased significantly compared with pre-operation (P<0.01). When local recurrence or distant metastasis presented, MDSCs percentage increased again (all P<0.01) and reached the preoperative level(P>0.05). All the patients were further divided into two groups based on median MDSCs percentage. Patients with higher MDSCs percentage before operation (>3.78%) and after operation (>2.11%) had significantly lower 5-year overall survival(OS) (58.1% and 62.1%) and 5-year disease-free survival (DFS)(54.8% and 58.6%) as compared to those with lower MDSCs percentage(5-year OS 87.9% and 84.8%; 5-year DFS 82.8% and 80.0%, all P<0.05). Multivariate analysis showed that preoperative MDSCs percentage was an independent prognostic factor of rectal cancer(HR:4.065, 95% CI:1.026 to 16.108, P=0.04). Preoperative increased MDSCs percentage may be an important predictor of poor OS in rectal cancer patients. Dynamic change of MDSCs percentage can reflect the disease development.

Discontinuation of hypomethylating agent therapy in patients with myelodysplastic syndromes or acute myelogenous leukemia in complete remission or partial response: Retrospective analysis of survival after long-term follow-up

Hypomethylating agents (HMA), such as 5-azacitidine or decitabine, are currently used to treat patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) until treatment failure. However, the outcomes for patients who discontinue therapy after achieving partial response (PR) or complete remission (CR) but before treatment failure have not been reported. We present a series of 16 patients with higher-risk MDS (n=5; 31%) or AML (n=11; 69%) who achieved PR (n=1) or CR (n=15) and stopped HMA therapy while in response in the context of clinical trials. They received a median of 12 courses (range 1–24) and achieved response after a median of 1 course of therapy (1–4). Loss of response after discontinuation of therapy was rapid, with a median progression-free survival of 4 months (95% CI: 2–6). Median overall survival (OS) from the time of therapy discontinuation was 15 months (95% CI: 6–24). Patients who received 12 cycles of therapy or more had significantly better OS (median: 20 months [95% CI: 12–27]) than those who received fewer than 12 cycles (median: 4 months [95% CI: 1–8]) (p=0.043). Poor-risk cytogenetics were also associated with lower 1-year OS (33% versus 69%; p=0.046). According to these results and considering the poor prognosis after HMA failure, HMA interruption should be avoided once a sustained response has been achieved.

Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas.

To refine stage and prognostic group for human papillomavirus (HPV) -related nonmetastatic (M0) oropharyngeal cancer (OPC). All patients with nonmetastatic (M0) p16-confirmed OPC treated with radiotherapy with or without chemotherapy from 2000 to 2010 were included. Overall survival (OS) was compared among TNM stages for patients with HPV-related and HPV-unrelated OPC separately. For HPV-related OPC, recursive partitioning analysis (RPA) derived new RPA stages objectively. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR stages. The performance of survival prediction of RPA stage and AHR stage was assessed against the current seventh edition TNM stages. Prognostic groups were derived by RPA, combining RPA stage and nonanatomic factors. The cohort comprised 573 patients with HPV-related OPC and 237 patients with HPV-unrelated OPC, with a median follow-up of 5.1 years. Lower 5-year OS with higher TNM stage was evident for patients with HPV-unrelated OPC (stage I, II, III, and IV 5-year OS: 70%, 58%, 50%, and 30%, respectively; P = .004) but not for patients with HPV-related OPC (stage I, II, III, and IV 5-year OS: 88%, 78%, 71%, and 74%, respectively; P = .56). RPA divided HPV-related OPC into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3; 5-year OS: 82%, 76%, and 54%, respectively; P < .001). AHR also yielded a valid classification, but RPA stage demonstrated better survival prediction. A further RPA (including RPA stage, age, and smoking pack-years [PYs]) derived the following four valid prognostic groups for survival: group I (T1-3N0-N2c_≤ 20 PY), group II (T1-3N0-N2c_> 20 PY), group III (T4 or N3_age ≤ 70), and group IVA (T4 or N3_age > 70; 5-year OS: 89%, 64%, 57%, and 40%, respectively; P < .001). An RPA-based TNM stage grouping (stage I/II/III: T1-3N0-N2b/T1-3N2c/T4 or N3, with M1 as stage IV) is proposed for HPV-related OPC as a result of significantly improved survival prediction compared with the seventh edition TNM, and prognostication is further improved by an RPA-based prognostic grouping within the American Joint Committee on Cancer/Union for International Cancer Control TNM framework for HPV-related OPC.

Interim FDG PET/CT for predicting the outcome in patients with head and neck cancer.

The study aimed to investigate the prognostic effects of interim (18) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) during definitive radiotherapy (RT) or chemoradiotherapy (CRT) in patients with head and neck cancer. This is a prospectively treatment study. The pretreatment and interim PET/CT images of 51 patients with advanced pharyngeal cancers receiving definitive RT/CRT were evaluated prospectively. The interim PET/CT images were taken at a cumulative RT dose ranging from 41.4 to 46.8 Gy. The maximum standardized uptake value (SUVm) of the interim PET/CT and the reduction ratio of the SUVm (SRR) between the two images were measured. The differences between patients with or without local failures were examined using the Mann-Whitney test. Overall survival (OS), disease-free survival (DFS), and primary and nodal relapse-free survival rates were calculated using the Kaplan-Meier method. Independent prognosticators were identified using Cox regression analysis. After a median follow-up duration of 23 months, a higher interim SUVm was associated with local failures. Conducting a multivariate analysis revealed that a SUVmax reduction ratio of primary tumor (SRR-P) < 0.64 was associated with the inferior OS (hazard ratio 2.64; P =0.035) and DFS (hazard ratio 2.33; P = 0.045). Patients who had tumors with an SRR-P < 0.64 had a considerably lower 2-year OS and DFS compared with those who had SRR-P ≥ 0.64 (47% vs. 66%; 41% vs. 64%). A higher interim SUVm was associated with local recurrence. In addition, patients with a lower SRR-P should be considered to be at risk of primary failure. 4.

Treatment patterns and affecting factors in breast cancer patients over 65-years of age

To explore different therapies and affecting factors in breast cancer patients ≥ 65 years old. To retrospectively analyze the clinical characteristics, treatments, comorbidity and survival rate of 126 female breast cancer patients over 65 years old who underwent surgical operation in our hospital from January 2009 to December 2010. To compare and analyze the differences in the treatment patterns, and find out the affecting factors. One hundred and twenty-six cases were included in this retrospective study, and they were divided into two groups according to age: 65-74 years old group (71 cases) and >74 years group (55 cases). Most patients in the two groups received modified radical mastectomy (84.5% and 89.1%); 73.2% and 54.5% of patients received adjuvant chemotherapy in the two groups, respectively. 67.6% and 61.8% of the patients had adjuvant endocrine therapy respectively. 19.7% and 7.3% of the patients received radiotherapy, respectively. Chemotherapy in elderly breast cancer patients was correlated with age, pathological types, progesterone receptor (PR) status and comorbidity. Radiotherapy in elderly breast cancer patients was related to age, surgical patterns, TNM stage and lymph node status. Multivariate analysis showed that age, pathological types, PR expression and comorbidity were independent factors affecting choice of chemotherapy in elderly breast cancer patients (P < 0.05 for all). Age and surgical patterns were independent factors affecting choice of radiotherapy (P < 0.05 for all). The 3-year disease-free survival (DFS) rate and overall survival (OS) rate in these patients were 91.3% and 92.0%, respectively. Furthermore, endocrine therapy was related to 3-year DFS rate (P = 0.038) and age was correlated with 3-year OS rate (P = 0.037) in these elderly patients. Breast cancer in the elderly patients receive similar surgery and endocrine therapy, but the elderly patients are less likely to have chemotherapy and radiotherapy, due to age, PR expression, pathological types, surgical patterns and comorbidity. Only age contributes to the lower 3-year overall survival rate in >74-year old patients.

Pretreatment metabolic tumor volumes to predict the short-term outcome of unresectable locally advanced squamous cell carcinoma of the esophagus treated with definitive chemoradiotherapy

The aim of the study was to investigate the predictive role of pretreatment metabolic tumor volume (MTV) in patients with squamous cell carcinoma of locally advanced esophageal cancer treated with definitive chemoradiotherapy. Ninety patients received pretreatment with (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT, and two types of MTVs were measured on the basis of either a maximal standardized uptake value (SUVmax) of 2.5 (MTV2.5) or a fixed threshold of 20% (MTV20%). Overall survival (OS) and disease-free survival (DFS) were examined, and independent prognosticators were identified by Cox regression analysis. On a median follow-up of 15 months, 51 patients were seen to have died because of tumor recurrence or other illnesses. Multivariate analysis of OS revealed that MTV20%>40 ml was the only predictor of outcome with a lower 1-year OS [P=0.003, hazard ratio (HR)=2.29, 95% confidence interval (CI) 1.36-3.91]. Two independent predictors of DFS were MTV20%>40 ml (P=0.02, HR=1.78, 95% CI 1.09-2.91) and stage IV disease (P=0.01, HR=1.84, 95% CI 1.12-3.03). Pretreatment MTV20% is a novel marker for OS and DFS in patients with unresectable locally advanced esophageal cancer treated with definitive chemoradiotherapy. Treatment intensification must be considered for patients with higher MTVs.