Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: An exploratory,retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG)

BackgroundAdult patients with advanced soft tissue sarcomas (STS) are generally treated similarly, regardless of great differences between STS subtypes, disease presentation and patients’ characteristics. As ifosfamide is frequently applied in first line systemic therapy, we aimed to establish prognostic and predictive factors for outcome to ifosfamide-based therapy.MethodsA retrospective, exploratory analysis was performed on data from 1337 advanced STS patients who received first-line ifosfamide-containing chemotherapy. For predictive factor analysis, 660 patients treated with doxorubicin monotherapy served as comparators.ResultsIndependent favourable prognostic factors for overall survival (OS) were good performance status, female gender, low histological grade, extremity primary tumour site and locally advanced disease; for progression-free survival (PFS), the combination of doxorubicin and ifosfamide, locally advanced disease, and tumour entity with a lower risk to progress for synovial sarcoma patients compared to leiomyosarcoma. For response, independent favourable prognostic factors were doxorubicin combined with ifosfamide, higher histological grade, and histology with synovial sarcoma patients having the highest chance to respond. Predictive factor analysis showed that compared to doxorubicin monotherapy, patients who benefited less from ifosfamide-based therapies were leiomyosarcoma patients in terms of OS, and patients with liposarcoma for response. No predictive factors were found for PFS.ConclusionIn this study, we established an independent set of prognostic and predictive factors for outcome to ifosfamide-based chemotherapy in advanced STS patients. This study provides important information for the interpretation and design of clinical trials for specific STS entities and may contribute to further treatment individualisation of advanced STS patients.     

Outcome of chemotherapy in advanced synovial sarcoma patients: Review of 15 clinical trials from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group; setting a new landmark for studies in this entity

IntroductionPrevious studies in metastatic soft tissue sarcomas (STS) showed that synovial sarcomas tend to have better survival rates and a higher chemosensitivity than other STS subtypes. However, data are derived from relatively small subgroups and statistical significance of these observations is lacking. Larger cohorts are necessary to define and confirm the specific characteristics of this subtype.Patients and methodsPatient data were retrieved from 15 European Organisation for Research and Treatment of Cancer advanced first-line STS trials. Patient characteristics, survival and treatment response of synovial sarcoma patients were compared to other STS patients. Univariable and multivariable analyses were performed to evaluate prognostic factors.ResultsIn total, 3330 advanced STS patients were retrieved, of whom 313 had a synovial sarcoma. Synovial sarcoma patients were significantly younger (median 40 versus 52 years), more often had extremity primary tumours and had a better performance status (PS 0: 50.2 versus 43.4%) compared to other STS patients. Additionally, synovial sarcoma patients had a significantly better response to chemotherapy (responders: 27.8 versus 18.8%) and better survival rates (progression free survival [PFS]: 6.3 versus 3.7 months; Overall survival [OS]: 15.0 versus 11.7 months). Age, PS, and presence of metastatic disease were defined as prognostic factors for PFS and OS in the univariable analysis. The last two factors were confirmed in the multivariable analysis for OS.DiscussionAdvanced synovial sarcomas are a distinct subgroup of STS, with a better response to systemic chemotherapy and longer PFS and OS. These results should be taken into account in the design of future synovial sarcoma specific studies.     

Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials

BackgroundThe EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT.Patients and methodsIndividual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor.ResultsA total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms.ConclusionAdjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.     

Validation of the prognostic relevance of plasma C-reactive protein levels in soft-tissue sarcoma patients

Background:

The concept of the involvement of systemic inflammation in cancer progression and metastases has gained attraction within the past decade. C-reactive protein (CRP), a non-specific blood-based marker of the systemic inflammatory response, has been associated with decreased survival in several cancer types. The aim of the present study was to validate the prognostic value of pre-operative plasma CRP levels on clinical outcome in a large cohort of soft-tissue sarcoma (STS) patients.

Methods:

Three hundred and four STS patients, operated between 1998 and 2010, were retrospectively evaluated. CRP levels and the impact on cancer-specific survival (CSS), disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan–Meier curves and univariate as well as multivariate Cox proportional models. Additionally, we developed a nomogram by supplementing the plasma CRP level to the well-established Kattan nomogram and evaluated the improvement of predictive accuracy of this novel nomogram by applying calibration and Harrell''s concordance index (c-index).

Results:

An elevated plasma CRP level was significantly associated with established prognostic factors, including age, tumour grade, size and depth (P<0.05). In multivariate analysis, increased CRP levels were significantly associated with a poor outcome for CSS (HR=2.05; 95% CI=1.13–3.74; P=0.019) and DFS (HR=1.88; 95% CI=1.07–3.34; P=0.029). The estimated c-index was 0.74 using the original Kattan nomogram and 0.77 when the plasma CRP level was added.

Conclusion:

An elevated pre-operative CRP level represents an independent prognostic factor that predicts poor prognosis and improves the predictive ability of the Kattan nomogram in STS patients. Our data suggest to further prospectively validate its potential utility for individual risk stratification and clinical management of STS patients.     

Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: subanalysis of two European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62043 and 62072

BackgroundPazopanib recently received approval for the treatment of certain soft tissue sarcoma (STS) subtypes. We conducted a retrospective analysis on pooled data from two EORTC trials on pazopanib in STS in order to characterize long-term responders and survivors.Patients and methodsSelected patients were treated with pazopanib in phase II (n = 118) and phase III study (PALETTE) (n = 226). Combined median progression-free survival (PFS) was 4.4 months; the median overall survival (OS) was 11.7 months. Thirty-six percent of patients had a PFS ≥ 6 months and were defined as long-term responders; 34% of patients survived ≥18 months, defined as long-term survivors. Patient characteristics were studied for their association with long-term outcomes.ResultsThe median follow-up was 2.3 years. Patient characteristics were compared among four subgroups based on short-/long-term PFS and OS, respectively. Seventy-six patients (22.1%) were both long-term responders and long-term survivors. The analysis confirmed the importance of known prognostic factors in metastatic STS patients treated with systemic treatment, such as performance status and tumor grading, and additionally hemoglobin at baseline as new prognostic factor. We identified 12 patients (3.5%) remaining on pazopanib for more than 2 years: nine aged younger than 50 years, nine females, four with smooth muscle tumors and nine with low or intermediate grade tumors at initial diagnosis. The median time on pazopanib in these patients was 2.4 years with the longest duration of 3.7 years.ConclusionsThirty-six percent and 34% of all STS patients who received pazopanib in these studies had a long PFS and/or OS, respectively. For more than 2 years, 3.5% of patients remained progression free under pazopanib. Good performance status, low/intermediate grade of the primary tumor and a normal hemoglobin level at baseline were advantageous for long-term outcome.NCT00297258 (phase II) and NCT00753688 (phase III, PALETTE).     

Prognostic significance of systemic immune-inflammation index-based nomogram for early stage hepatocellular carcinoma after radiofrequency ablation

BackgroundRadiofrequency ablation (RFA) is the recommended treatment for early stage hepatocellular carcinoma (HCC), and the prognostic value of systemic immune-inflammation index (SII) in early stage HCC is not discussed. Therefore, the purpose of the study is to explore the prognostic value of SII based on lymphocyte, neutrophil, and platelet counts in patients with HCC after RFA.MethodsWe retrospectively evaluated the prognostic value of the SII in training and validation cohorts, and then established an effective nomogram for HCC after RFA based on SII. The C-index, and area under the time-dependent receiver operating characteristic curve (t-AUC) were used to evaluate the discrimination and calibration value of the nomogram.ResultsAn optimal cut-off value for the SII of 324.55×10⁹ stratified the patients with HCC into high- and low-SII groups. Univariate and multivariate analyses revealed that SII was an independent predictor for overall survival (OS) and recurrence-free survival (RFS). Moreover, SII was an independent prognostic factor for early-stage HCC with normal alpha-fetoprotein (AFP) levels. The t-AUC of the SII was higher for OS and RFS than for neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). A high preoperative SII was associated with multiple tumors, larger tumors, and higher levels of AFP. A well-discriminated and calibrated nomogram was constructed to predict the probability of 1-, 2-, 3-, and 5-year RFS with C-indexes of 0.80, which was significantly higher than that obtained with other prognostic clinical indexes.ConclusionsThe SII is an independent prognostic factor affecting the survival outcomes of patients with early-stage HCC. The comprehensive nomogram based on SII presented in this study is a promising model for predicting RFS in HCC patients after RFA.     

Prognostic value of pre-operative systemic immune-inflammation index and platelet to lymphocyte ratio in peritoneal carcinomatosis of ovarian origin

Background and objectivesThe aim of this study was to investigate the impact of systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) on the survival outcomes of patients who underwent to cytoreductive surgery (CRS) and HIPEC for ovarian peritoneal carcinomatosis.MethodsA retrospective analysis of 68 cases following surgery at our department between 2015 and 2020 was performed. Receiver Operating Characteristic (ROC) curve was used with Youden index to calculate the optimal cutoff values for SII, PLR and NLR.ResultsUnivariate analysis revealed that high preoperative values of SII, PLR and NLR were correlated with worse overall survival (OS) and disease-free survival (DFS) in these patients. In the multivariable analysis, high SII was recognized as an independent prognostic factor for OS (CI 95%: 0.002- 3.835, p = 0.097) and high PLR was recognized as an independent prognostic factor for DFS (CI 95%: 0.253–2.248, p = 0.007).ConclusionSII and PLR could be useful prognostic tools to predict outcomes of patients who underwent to CRS and HIPEC for ovarian peritoneal carcinomatosis.     

A prognostic nomogram for colorectal cancer liver metastases after percutaneous thermal ablation

Purpose: To assess the efficacy of percutaneous thermal ablation in treating colorectal cancer liver metastases (CRCLM), and to propose a prognostic nomogram for overall survival (OS).

Materials and methods: Seventy-one patients with CRCLM undergoing thermal ablation at our institute from 2009 to 2013 were identified and analysed to formulate a prognostic nomogram. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the nomogram. The nomogram was compared with two current prognostic nomograms for patients with CRCLM who had undergone hepatectomy (Kattan) and selective internal radiation therapy (Fendler). Predictive validity was assessed in the validation cohort of 25 patients who had undergone thermal ablation from 2014 to 2016.

Results: The median OS in the primary cohort was 26.4?months, whereas the 1-, 3- and 5-year OS rates were 72.2%, 37.2% and 17%, respectively. The median progression-free survival was 4.2?months. After univariate and multivariate analysis, a prognostic nomogram was formulated based on four predictors, including the number of tumours, maximum diameter of the tumour, CA19–9 level and ablation margin. The C-index of the nomogram was 0.815. Based on the patients of this study, the C-index was significantly higher than that of the Fendler nomogram (C-index, 0.698) and Kattan nomogram (C-index, 0.514, p?Conclusions: Thermal ablation was an effective therapy for CRCLM. Moreover, the nomogram was effective and simple for CRCLM patients undergoing thermal ablation.     

Predictive Impact of The Inflammation-based Indices in Uveal Melanoma Liver Metastases Treated with Transarterial Hepatic Chemoperfusion

BackgroundThe aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion.Patients and methods54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1–11) treatment sessions were performed with melphalan (92%) or fotemustin (8%). Inflammatory indices were calculated as follows: neutrophils/nl to lymphocytes/nl ratio (NLR), systemic immune-inflammation index ([platelets/nl × neutrophils/nl]/[lymphocytes/nl]; SII), and platelets/nl to lymphocytes/nl ratio (PLR). The cut-off for dichotomization purposes was set at the median (inflammatory indices, hepatic tumor burden) or the upper level of normal. Kaplan Meier analysis was performed for median overall survival (OS) in months, and Cox proportional hazard model for uni(UVA) and multivariate (MVA) hazard ratio (HR, 95%CI) analyses were performed.ResultsMedian OS of the study cohort was 7.7 (6.3–10.9) months. In UVA OS was prolonged for low C reactive protein (CRP) (13.5 vs. 5.2; p = 0.0005), low SII (10.8 vs. 5.6; p = 0.0005), low NLR (11.1 vs. 6.3; p = 0.0045), low aspartate aminotransferase (AST) (11.5 vs. 5.6; p = 0.015), alanine aminotransferases (ALT) (11.5 vs. 5.6; p = 0.01), and tumor burden ≦ 50% (8.2 vs. 4.8; p = 0.007). MVA confirmed low CRP (HR: 0.29, 0.11–0.7; p = 0.005), low SII (HR: 0.19, 0.11–0.7; p = 0.008), and low ALT (HR: 0.13, 0.02–0.63; p = 0.011) as independent predictors for prolonged OS. Patients with ≦ 1, 2, 3 elevated significant MVA-factors survived a median of 14.9, 7.7, and 3.9 months, respectively (p = 0.0001).ConclusionsPretreatment inflammatory markers (CRP, SII) and AST were independent prognostic survival markers in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. A combination of factors may help to identify patients potentially benefitting from treatment.Key words: uveal melanoma, liver metastases, transarterial hepatic chemoperfusion, melphalan, inflammatory markers     

Advanced soft-tissue sarcoma in elderly patients: patterns of care and survival

BackgroundThere are no data regarding the management of advanced soft-tissue sarcoma (STS) in elderly patients.Patients and methodsWe retrospectively reviewed the charts of patients ≥75 years old diagnosed with metastatic or unresectable STS between 1991 and 2011 in 11 French and American centers.ResultsThe study included 361 patients. Of these, 223 patients (62%) received systemic therapy, whereas 123 patients (34%) were managed with best supportive care (BSC) only. Patients who received BSC were more likely to be ≥80 years, with performance status (PS) ≥ 2, Charlson comorbidity score ≥ 10, and metastatic disease. The median progression-free survival of patients treated with systemic therapy was 4 months (95% CI: 2.9–5.1). Thirty-six patients (16%) stopped chemotherapy because of toxicity. Median overall survival (OS) of patients managed with specific therapy was 10.9 months (95% CI: 8.3–13.5) versus 5.3 months (95% CI: 3.6–7.1) for patients managed with BSC (P = 0.001). On multivariate analysis, age ≥ 80 years, PS ≥ 2, and number of metastatic sites were the only independent factors associated with OS.ConclusionA high proportion of elderly patients with advanced STS were denied chemotherapy. Further efforts are needed to define better the optimal care for fit and unfit elderly patients with STS.     

Risk factors in germ cell tumour patients with relapse or progressive disease after first-line chemotherapy: evaluation of a prognostic score for survival after high-dose chemotherapy

PurposeTo retrospectively re-evaluate a published prognostic score for response to salvage treatment in patients with germ-cell tumours relapsing or progressing after cisplatin-based first-line chemotherapy.Patients and methodsFrom a database of 257 germ cell tumour (GCT) patients treated with salvage high-dose chemotherapy (HDCT) we identified 176 patients (67%) with relapse or progression after first-line conventional-dose chemotherapy (CDCT). Patients were retrospectively grouped according to a published prognostic score defined by Fossa and colleagues [Fossa SD, Stenning SP, Gerl A, et al. Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumors. Br J Cancer 1999; 80:1392–9]. Overall survival (OS) and event free survival (EFS) after HDCT were retrospectively evaluated in each prognostic group.ResultsAfter a median follow-up of 9 years the OS probability for all 176 patients was 38% and the EFS probability was 35%. The respective survival probability at 5 years in 100/176 (57%) good prognosis patients and 76/176 (43%) poor prognosis patients were 47% versus 28% for OS (p < 0.001) and 41% versus 26% for EFS (p < 0.005). Whereas survival probabilities did not differ in good prognosis patients, OS and EFS in poor prognosis patients were substantially better in the current series of patients treated with HDCT compared to the ones reported by Fossa treated with CDCT.ConclusionThis retrospective analysis confirms the impact of prognostic factors on the results of salvage treatment in patients with GCT and suggests a clinical benefit for patients with poor prognosis features receiving a single course of HDCT.     

Multicentre validation of a clinical prognostic score integrating the systemic inflammatory response to the host for patients treated with curative-intent for colorectal liver metastases: The Liverpool score

BackgroundThis study aimed to create a new prognostic score integrating the systemic inflammatory response to predict survival in patients treated with curative intent for colorectal liver metastases (CLM).MethodsWe identified independent prognostic factors in patients who underwent liver surgery for CLM in a tertiary centre in the United Kingdom (UK) between 2010 and 2015. A pre- and a postoperative score (Liverpool score) were created by combining these factors to stratify patients into different risk groups. These new scores were validated in an international cohort of 219 patients from China and France.ResultsMultivariate cox regression analysis of the 364 patients of the UK cohort identified 6 preoperative and 1 postoperative prognostic factors for overall survival (OS): American society of anaesthesiologists (ASA) score, location and node status of the primary tumour, number and size of CLM, neutrophil-to-lymphocyte ratio (NLR) and resection margin. Both pre- and postoperative scores can be calculated with an online calculator at https://jscalc.io/calc/PXatrmjfrEFpYy2t. Using the pre-operative model on the UK cohort, median OS was 61.22 (50.23, not reached) months in the low-risk group (n = 162) and 30.36 (23.68, 35.95) months in the high-risk group (n = 162, p < 0.0001). The same difference was observed in the validation cohort. The Liverpool score outperformed previously published scoring system with a c-index of 0.619 pre-operatively and of 0.637 post-operatively.ConclusionWe developed a new prognostic score based on clinicopathologic characteristics including the site of the primary tumour location and on measurement of the systemic inflammatory response which could help to tailor patients’ management.     

Early recurrence in peritoneal metastasis of appendiceal neoplasm: Survival and prognostic factors

IntroductionEarly recurrence (ER) is defined as development of loco-regional peritoneal disease within 12-month of the initial CRS/PIC. Our aims were to identify overall survival (OS), recurrence-free survival (RFS) and independent prognostic factors associated with ER in PM of appendiceal neoplasm.Materials and methodsA prospectively-maintained database for patients with appendiceal neoplasm undergoing cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) from year 1996–2018 was retrospectively analysed.Results208 female and 185 male patients were identified. With a median follow-up of 40-month, 40.2% of the patients developed ER. The median OS for ER was 24 months compared to late (LR) at 64 months. Median OS was not reached in non-recurrence (NR). 5-year survival for ER was less favourable compared to LR and NR (19.3%vs54.6%vs94%). No patients in ER group survived beyond 10-year. Independent negative predictors associated with ER on multivariate analysis were male patient (p = 0.013), blood transfusion of >8 units (p = 0.013), elevated preoperative CEA levels (>5 ng/ml; p = 0.002) and hard intraoperative tumour consistency (p < 0.001). Protective factor was a combination of CC1, hard tumour consistency and use of EPIC (p = 0.039). Independent prognostic factors that predicted recurrence of appendiceal PM were PCI >20 (p = 0.049), non-use of EPIC (p = 0.012), hard tumour consistency (p = 0.004) and use of previous chemotherapy (p = 0.023).ConclusionER following CRS and PIC of appendiceal PM is associated with reduced survival outcomes. Our data alludes to the importance of optimising the risk factors in order to delay loco-regional recurrence and improve long-term survival of these patients.     

A nomogram prognostic index for risk-stratification in diffuse large B-cell lymphoma in the rituximab era: a multi-institutional cohort study

Background We aimed to establish a predictive prognostic risk-stratification model for diffuse large B-cell lymphoma (DLBCL) in the rituximab era.Methods The data of 1406 primary DLBCL patients from the Sun Yat-Sen University Cancer Center were analysed to establish a nomogram prognostic index (NPI) model for predicting overall survival (OS) based on pre-treatment indicators. An independent cohort of 954 DLBCL patients from three other hospitals was used for external validation.Results Age, performance status, stage, lactate dehydrogenase, number of extranodal sites, BCL2, CD5 expression, B symptoms and absolute lymphocyte and monocyte count were the main factors of the NPI model and could stratify the patients into four distinct categories based on their predicted OS. The calibration curve demonstrated satisfactory agreement between the predicted and actual 5-year OS of the patients. The concordance index of the NPI model (0.794) was higher than the IPI (0.759) and NCCN-IPI (0.750), and similar results were obtained upon external validation. For CD5 + DLBCL patients, systemic treatment with high-dose methotrexate was associated with superior OS compared to R-CHOP-based immunochemotherapy alone.Conclusions We established and validated an accurate prediction model, which performed better than IPI and NCCN-IPI for prognostic stratification of DLBCL patients.Subject terms: B-cell lymphoma, Cancer models     

Stereotactic radiotherapy for oligometastatic cancer: a prognostic model for survival

BackgroundStereotactic radiotherapy (SRT) is a safe and locally effective treatment for patients with inoperable oligometastases. The challenge remains identifying subsets of patients that benefit in terms of overall survival (OS).Patients and methodsBetween 2005 and 2011, 309 patients with ≤5 metastases were treated by stereotactic body radiotherapy (n = 209) and/or by intracranial single or fractionated stereotactic radiotherapy (n = 107). We analyzed OS and carried out a risk factor analysis.ResultsThe median survival of all patients was 24 months. The 3-, 4- and 5-year OS rates were 32%, 25% and 19%, respectively. The following four risk factors were independently associated with impaired OS: nonadenocarcinoma histology (P < 0.01), intracranial metastases (P < 0.01), synchronous oligometastatic disease (P < 0.01) and male gender (P = 0.02). Patients with 0, 1 and 2 risk factors displayed a median survival (95% CI) of 40 (24–63), 29 (23–35) and 23 (16–29) months, respectively, and are defined as patients with good prognosis. Patients with 3 and 4 risk factors had a median survival of 9 (6–11) and 4 (1–7) months only and are defined as bad prognostic patients.ConclusionsWe identified subsets of oligometastatic cancer patients with good prognosis after SRT. These patients are candidates for inclusion in prospective randomized trials for defining the role of SRT in the management of oligometastases.     

Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in metastatic breast cancer

IntroductionLymphocytopenia and circulating tumor cells (CTCs) have been reported as independent prognostic factors for overall survival (OS) in metastatic breast cancer (MBC), and both have been associated with bone metastases. Our objective was to compare the prognostic significance of lymphocytopenia, CTC count, and extensive bone metastases (> 2 lesions) assessed by fluorine-18 (¹⁸F) fluorodeoxyglucose positron emission tomography/computed tomography (FDG–PET/CT) in patients with MBC.Patients and MethodsThis is a retrospective study that included patients with MBC who were starting a new line of systemic therapy. The study population consisted of patients treated at the University of Texas MD Anderson Cancer Center between 2004 and 2008 for whom baseline CTC count, lymphocyte counts, and FDG–PET/CT scans were available. Patients were stratified according to estrogen receptor status (positive vs. negative), human epidermal growth factor receptor 2 (HER2) status (amplified vs. constitutive), baseline CTC counts per 7.5 mL of blood (< 5 CTCs/7.5 mL of blood vs. ≥ 5 CTCs/7.5 mL of blood), lymphocytopenia (< 1000 vs. ≥ 1000/μL), and extensive bone metastases (> 2 vs. ≤ 2 lesions).ResultsIn 195 assessable patients, the median OS was 27 months (range, 1 to > 45 months). In multivariate analysis, lymphocytopenia, ≥ 5 CTCs/7.5 mL of blood, estrogen receptor status, and line of therapy were the only predictive factors for progression-free survival (PFS) (2P = .001, 2P = .032, 2P = .029, and 2P = .002, respectively) and OS (2P = .001, 2P = .009, 2P = .004, and 2P = .024, respectively).ConclusionCTC measurement and lymphocytopenia are independent prognostic factors for PFS and OS in patients with MBC.     

Comorbidity as prognostic variable in MDS: comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS Study Group

BackgroundThe evaluation of comorbidity is of increasing importance in patients with hematologic disorders.Patients and methodsIn the present study, the influence of comorbidity on survival and acute myeloid leukemia (AML) evolution was analyzed retrospectively in 419 patients with de novo myelodysplastic syndromes (MDS) (observation period: 1985–2007). The median age was 71 years (range 24–91 years). Two different scoring systems, the hematopoietic stem-cell transplantation-specific comorbidity index (HCT-CI) and the Charlson comorbidity index (CCI) were applied.ResultsThe HCT-CI was found to be a significant prognostic factor for overall survival (OS, P < 0.05) as well as event-free survival (EFS, P < 0.05) in our patients, whereas the CCI was of prognostic significance for OS (P < 0.05), but not for EFS. For AML-free survival, neither the HCT-CI nor the CCI were of predictive value. A multivariate analysis including age, lactate dehydrogenase, ferritin, karyotype, number of cytopenias, French–American–British groups, and comorbidity was applied. Comorbidity was found to be an independent prognostic factor in patients with low- or int-1-risk MDS (P < 0.05) regarding OS and EFS.ConclusionsTogether, our data show that comorbidity is an important risk factor for OS and EFS in patients with MDS.     

The prognostic significance of left ventricular ejection fraction in patients with advanced cancer treated in phase I clinical trials

BackgroundNew targeted agents may cause acute cardiac events. The purpose of our study was to investigate the incidence and the prognostic significance of left ventricular ejection fraction (LVEF) in phase I trials.Patients and methodsBetween October 2008 and September 2011, the records of 1166 consecutive patients with advanced cancer treated in the Phase I Clinic who underwent echocardiography were retrospectively reviewed.ResultsMost of the patients were White (78%), and the most common tumor types were colorectal cancer and melanoma. Of 1166 patients, 177 (15.2%) patients had an LVEF of <50%. No difference in overall survival (OS) between patients with LVEF ≥ 50% and patients with LVEF < 50% was seen (median OS 7.4 versus 7.0 months, P = 0.84). Patients with LVEF ≤ 35% had shorter survival compared with those with LVEF between 35% and 50% (median 4.2 versus 8.0 months; P = 0.005). In multivariate analysis of patients with LVEF < 50%, independent factors predicting longer survival were LVEF > 35%, ≤2 prior systemic therapies, ≤2 metastatic sites, and normal lactate dehydrogenase and albumin levels.ConclusionEchocardiography would improve patient selection for enrollment in phase I clinical trials. These data suggest that it is safe to treat patients with LVEF between 35% and 50%.     

Lymphoma occurring in patients over 90 years of age: characteristics,outcomes, and prognostic factors. A retrospective analysis of 234 cases from the LYSA

BackgroundLymphoma occurring in patients aged 90 or older is not uncommon, and its incidence is expected to increase over time. Management of these patients is difficult given their underlying fragility and the lack of information regarding this population.Patients and methodsWe retrospectively analyzed 234 patients diagnosed with lymphoma at the age of 90 years or older (90+) between 1990 and 2012 to describe their characteristics, management, outcomes and prognostic factors.ResultsThe median age was 92 years; 88% were B-cell lymphomas consisting mainly in diffuse large B-cell lymphoma. The median overall survival (OS) was 7.2 months (range, 0–92 months) for the 227 patients with non-Hodgkin Lymphoma (NHL), with a significant difference between aggressive and indolent NHL (5.2 months versus 19.4 months, respectively). We further analyzed 166 NHL patients for whom detailed characteristics were available. Among these patients, 63.5% received a treatment, either local (7.5%) or systemic (56%). Lymphoma was reported as the main cause of death (40%). Treatment administration was associated with improved OS in patients with aggressive (P < 0.001) but not indolent NHL (P = 0.96). In patients with aggressive NHL, hypoalbuminemia appeared as a strong and independent negative prognostic factor.ConclusionsThe median OS is short in 90+ patients diagnosed with lymphoma but some patients experience prolonged survival. Lymphoma represents the main cause of death in these patients. Treatment may improve survival of selected patients with aggressive but not indolent NHL. Management of these patients may be guided by prognostic factors identified in this study, notably serum albumin.     

Prognostic value of systemic immune-inflammatory index in survival outcome in gastric cancer: a meta-analysis

BackgroundIn recent years, many studies have reported that the systemic immune-inflammatory index (SII) can be used to predict the prognosis of cancer patients; however, this finding remains controversial in gastric cancer (GC). Therefore, the purpose of this study was to systematically and comprehensively probe the prognostic role of SII in GC.MethodsRelevant publications were extracted from PubMed, EMBASE, Cochrane Library databases, and WANFANG DATA (Chinese database). The included studies had patients with pathologically confirmed GC and long-term follow-up data. The patient''s outcome was death, recurrence, or status at the end of follow-up. The studies included randomized controlled tests, case-control studies, or cohort studies using a multivariate proportional hazard model adjusted for survival outcomes. Cochran’s Q test and Higgins’ I-squared statistic were performed to assess heterogeneity. Publication bias was assessed by visual inspection of a Begg’s funnel plot.ResultsA total of 6,925 patients in 11 studies were included. The pooled hazard ratio (HR) indicated that a higher SII value was significantly associated with worse overall survival (OS) [HR: 1.53, 95% confidence interval (CI): 1.27–1.83] and worse disease-free survival (DFS) (HR: 1.57, 95% CI: 1.24–1.97) in GC patients. In the subgroup analysis, the HR was 1.72 (95% CI: 1.51–1.95) and 1.27 (95% CI: 0.96–1.67) in the group of patients aged <59 and ≥59 years, respectively.ConclusionsThe pooled HR indicates that a higher SII in younger patients with GC predicts a poor prognosis. In elderly patients with GC, the prognostic role of SII needs further research.