Adverse Factors For Progression-free Survival Research Articles

The Potential Prognostic Value of Dual-Imaging PET Parameters Based on 18F-FDG and 18F-OC for Neuroendocrine Neoplasms.

Background To identify parameters based on dual-imaging 18F-AlF-NOTA-octreotide (18F-OC) and 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) for predicting the prognosis of neuroendocrine neoplasms (NENs). Materials and Methods Sixty-six patients (age: mean ± standard deviation (SD): 51.8 ± 11.8 years) who underwent both 18F-OC and 18F-FDG PET/CT imaging were enrolled in our retrospective study. The following PET parameters were measured: the maximum standardized uptake value (SUVmax) and the volumetric parameters—18F-OC SSR-derived tumor volume (TV) and somatostatin receptor expression (SRE, TV multiplied by the mean standardized uptake value (SUVmean)) and the 18F-FDG-derived multiple tumor volume (MTV) and tumor lesion glycolysis (TLG). The NETPET grade based on dual-imaging PET images was assessed. Progression-free survival (PFS) was set as an endpoint. Univariate and multivariate survival analyses were performed for PET parameters and clinical tumor data. Results In the univariate survival analyses of clinical information, PFS was significantly associated with age (>45.5 vs ≤45.5, years, P < 0.034) and the presence of bone metastases (P = 0.04). Higher values for the 18F-FDG and 18F-OC volumetric parameters and the NETPET grade were adverse factors for PFS according to the dual-imaging PET parameters. In the multivariate survival analysis, the NETPET grade and SRE were predictors of PFS in NEN patients. Conclusion The NETPET grade is a potential noninvasive prognostic biomarker for NENs.

Surgical management and long-term outcomes of intracranial giant cell tumors: a single-institution experience with a systematic review.

Intracranial giant cell tumors (GCTs) are extremely rare neoplasms with dismal survival and recurrence rates. The authors aimed to confirm independent adverse factors for progression-free survival (PFS) and to propose an optimal treatment algorithm. The authors reviewed the clinical data of 43 cases of intracranial GCTs in their series. They also reviewed 90 cases of previously reported GCTs in the English language between 1982 and 2017 using Ovid MEDLINE, Embase, PubMed, and Cochrane databases with keywords of "giant cell tumor" or "osteoclastoma" and "skull," "skull base," "temporal," "frontal," "sphenoid," or "occipital." These prior publication data were processed and used according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Aforementioned risk factors for the authors' series and the pooled cases were evaluated in patients not lost to follow-up (m = 38 and n = 128, respectively). The authors' cohort included 28 males and 15 females with a mean age of 30.5 years. Gross-total resection (GTR) was achieved in 15 (34.9%) patients. Fifteen patients (39.5%) who did not undergo GTR received postoperative radiotherapy with a mean total dose of 54.7 ± 4.1 Gy. After a mean follow-up of 71.3 months, 12 (31.6%) patients experienced recurrence, and 4 (10.5%) died of disease. The actuarial 5-year PFS and overall survival (OS) were 68.6% and 90.0% in the authors' cohort, respectively. A multivariate Cox regression analysis verified that partial resection (HR 7.909, 95% CI 2.296-27.247, p = 0.001), no radiotherapy (HR 0.114, 95% CI 0.023-0.568, p = 0.008), and Ki-67 ≥ 10% (HR 7.816, 95% CI 1.584-38.575, p = 0.012) were independent adverse factors for PFS. Among the 90 cases in the literature, GTR was achieved in 49 (54.4%) cases. Radiotherapy was administered to 33 (36.7%) patients with a mean total dose of 47.1 ± 5.6 Gy. After a mean follow-up of 31.5 months, recurrence and death occurred in 17 (18.9%) and 5 (5.6%) cases, respectively. Among the pooled cases, the 5-year PFS and OS were 69.6% and 89.2%, respectively. A multivariate model demonstrated that partial resection (HR 4.792, 95% CI 2.909-7.893, p < 0.001) and no radiotherapy (HR 0.165, 95% CI 0.065-0.423, p < 0.001) were independent adverse factors for poor PFS. GTR and radiotherapy were independent favorable factors for PFS of intracranial GCTs. Based on these findings, GTR alone or GTR plus radiotherapy was advocated as an optimal treatment; otherwise, partial resection plus radiotherapy with a dose ≥ 45 Gy, if tolerable, was a secondary alternative. Lack of randomized data of the study was stressed, and future studies with larger cohorts are necessary to verify these findings.Systematic review no.: CRD42018090878 (crd.york.ac.uk/PROSPERO/).

18F-FDG PET Dissemination Features in Diffuse Large B-Cell Lymphoma Are Predictive of Outcome.

We assessed the predictive value of new radiomic features characterizing lesion dissemination in baseline 18F-FDG PET and tested whether combining them with baseline metabolic tumor volume (MTV) could improve prediction of progression-free survival (PFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Methods: From the LNH073B trial (NCT00498043), patients with advanced-stage DLCBL and 18F-FDG PET/CT images available for review were selected. MTV and several radiomic features, including the distance between the 2 lesions that were farthest apart (Dmaxpatient), were calculated. Receiver-operating-characteristic analysis was used to determine the optimal cutoff for quantitative variables, and Kaplan-Meier survival analyses were performed. Results: With a median age of 46 y, 95 patients were enrolled, half of them treated with R-CHOP biweekly (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and the other half with R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone), with no significant impact on outcome. Median MTV and Dmaxpatient were 375 cm3 and 45 cm, respectively. The median follow-up was 44 mo. High MTV and Dmaxpatient were adverse factors for PFS (P = 0.027 and P = 0.0003, respectively) and for OS (P = 0.0007 and P = 0.0095, respectively). In multivariate analysis, only Dmaxpatient was significantly associated with PFS (P = 0.0014) whereas both factors remained significant for OS (P = 0.037 and P = 0.0029, respectively). Combining MTV (>384 cm3) and Dmaxpatient (>58 cm) yielded 3 risk groups for PFS (P = 0.0003) and OS (P = 0.0011): high with 2 adverse factors (4-y PFS and OS of 50% and 53%, respectively, n = 18), low with no adverse factor (94% and 97%, n = 36), and an intermediate category with 1 adverse factor (73% and 88%, n = 41). Conclusion: Combining MTV with a parameter reflecting the tumor burden dissemination further improves DLBCL patient risk stratification at staging.

Proposed Treatment Paradigm for Intracranial Chondrosarcomas Based on Multidisciplinary Coordination

Objectives There was no consensus regarding the treatment of intracranial chondrosarcoma (CSA). The study aimed to evaluate the adverse factors for progression-free survival (PFS) and overall survival (OS), and propose a treatment strategy for CSA.

Proposed Treatment Paradigm for Intracranial Chondrosarcomas Based on Multidisciplinary Coordination.

There was no consensus regarding the treatment of intracranial chondrosarcoma (CSA). The study aimed to evaluate the adverse factors for progression-free survival (PFS) and overall survival (OS) and to propose a treatment strategy for CSA. The clinical chart and radiographic data of 106 consecutive cases (mesenchymal and conventional CSA in 18 and 88 patients, respectively) of surgically treated CSAs were retrospectively reviewed. Gross total resection was achieved in 43 patients (40.6%), and adjuvant radiotherapy was administered in 45 patients. After a mean follow-up duration of 47.8 months, 38 patients (37.3%) experienced recurrence. PFS and disease-specific OS at 5 years was 57.7% and 74.4%. Independent adverse factors for PFS were previous surgery (hazard ratio [HR] 2.261; P= 0.028), increased lesion size (HR, 1.298; P= 0.026), extent of surgical resection (HR, 3.226; P < 0.001), malignant pathology (HR, 2.018; P= 0.003), and postoperative radiotherapy (HR, 3.246; P= 0.001). The stereotactic radiosurgery subgroup presented best 5-year PFS of 88.9%, and a linear accelerator prolonged the mean PFS time (57.0 months) compared with no radiation (38.1 months). In the incomplete resection subgroup (n=63), radiotherapy significantly benefited tumor control (HR, 2.101; P= 0.016). Extent of surgical resection (HR, 1.797; P= 0.026) and malignant disease (HR, 1.717; P=0.030) were associated with OS. Intracranial CSAs were not completely amendable by surgery alone. Gross total resection as far as possible plus radiation were necessary for mesenchymal CSA and conventional CSA with active growth or residual tumor. Stereotactic radiosurgery was an alternative if proton therapy was unavailable. A future study with a large cohort is required to verify our findings.

Surgical Management and Outcomes of Intracranial Chondromas: a Single-Center Case Series of 66 Patients.

Management of intracranial chondromas (ICDs) is difficult. This study aims to propose a tailored management strategy based on our management of ICDs. A retrospective review was performed in 66 patients who received surgical operations at our institute. Clinical charts and radiographs were reviewed, follow-up was performed, and adverse factors for progression-free survival (PFS) and overall survival were evaluated. The preoperative and postoperative Karnofsky performance status was 81.8 and 72.3, respectively. The mean tumor size was 3.5 cm. Gross total resection was achieved in 15 patients (22.7%). Six patients (10.3%) received postoperative radiation. After a mean follow-up duration of 85.5 months, recurrence occurred to 15 patients (28.8%) with surgery alone, and no recurrence was observed in patients receiving postoperative radiotherapy. Six patients (10.3%) died due to tumor progression. The risk factors affecting the PFS included age <33 years (hazard rate [HR] 6.876; 95% confidence interval [CI] 1.599-29.560; P= 0.010), tumor size ≥3.1 cm (HR 6.138; 95% CI 1.259-29.926; P= 0.025), tumor with evident atypia/mitotic activity (HR 4.672; 95% CI 1.352-16.152; P= 0.015), and partial resection (HR 12.841; 95% CI 3.004-54.896; P = 0.001). In all patients, the PFS rate was 75% at 5 years and 64% at 10years; in addition, the overall survival rate was 93% at 5 years and 83% at 10 years. The therapeutic strategy for ICDs should be individualized and should consider preoperative variables. Gross total resection was attempted if the tumors were resectable; otherwise, subtotal resection was an alternative. In patients with partial resection and evident atypia/mitotic activity, consultation with an oncologist for radiotherapy was recommended.

Prognostic significance of HLA class I and II expression in patients with diffuse large B cell lymphoma treated with standard chemoimmunotherapy.

Loss of tumor cell human leukocyte antigen (HLA) is an immune escape mechanism for malignancies. However, the effect of low HLA class I or class II expression in diffuse large B cell lymphoma (DLBCL) treated with chemoimmunotherapy with the monoclonal antibody rituximab is largely unknown. We retrospectively analyzed samples and other data from 144 patients with DLBCL who were newly diagnosed in our institution and treated with standard R-CHOP therapy. We used antibodies against pan-HLA class I and pan-HLA class II molecules to assess HLA expression and its effect on prognosis. In a multivariate analysis, loss of HLA class II expression was a significantly independent adverse factor for progression-free survival (PFS; hazard ratio 2.3; 95% confidence interval 1.2-4.6; P=0.01). Although HLA class I loss of expression did not correlate with prognosis, the combination of HLA class I(+) with either low peripheral lymphocyte count or CD3(+) lymphocyte count was an adverse prognostic factor for PFS. Loss of HLA class II is an International Prognostic Index (IPI)-independent adverse factor for PFS in patients with DLBCL treated with standard therapy. However, in contrast to other solid cancers, HLA class I loss was not solely a prognostic factor in DLBCL.

Diffuse large B-cell lymphoma of the breast: prognostic factors and treatment outcomes.

BackgroundThe breast is a rare site of extranodal involvement of diffuse large B-cell lymphoma (DLBCL). We aimed to assess the clinical characteristics, prognostic factors, and treatment outcomes of breast DLBCL.Patients and methodsWe retrospectively analyzed 113 patients (from our institution and the literature) between 1973 and 2014. The primary end point was overall survival (OS). Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was applied to determine the prognostic factors for OS, progression-free survival (PFS), local control (LC), and cause-specific survival (CSS).ResultsA total of 113 patients were included in the study: 42 cases from our hospital and 71 cases from 12 publications. The median age at diagnosis was 58 years. With a median follow-up time of 39.2 months, the estimated 5-year OS, PFS, LC, and CSS were 71.4%, 58.8%, 75.6%, and 74.9%, respectively. In multivariate analysis, more than four cycles of chemotherapy, having localized cancer, lumpectomy with or without axillary lymph node (ALN) dissection, and low to low-to-intermediate International Prognostic Index were favorable factors for OS. For PFS, significant prognostic factors were rituximab use, B symptoms, and tumor size. As for the local group, lumpectomy with or without ALN dissection and more than four cycles of chemotherapy were favorable factors for OS. Tumor size >4 cm and nonuse of rituximab were adverse factors for PFS. Twenty-one patients (18.6%) developed local relapse and 33 (29.2%) developed systemic relapse. Eight patients had central nervous system relapse (7.3%).ConclusionOur results reveal that local and extended staging criteria can reflect the different prognosis and treatment outcomes of breast DLBCL. Rituximab use, lumpectomy, and more than four cycles of chemotherapy are recommended as a treatment regimen. However, further study is warranted to validate our data.

Circulating tumor cells are predictive of poor response to chemotherapy in metastatic gastric cancer.

The aim of this study was to investigate the impact of number of circulating tumor cells (CTCs) on the treatment outcome for metastatic gastric cancer (GC) following palliative chemotherapy. CTCs were isolated from 7.5 mL of whole blood from 100 patients with metastatic GC by anti-EpCAM antibody coated magnetic particles using the CTC-Profiler (Veridex). Correlations between CTC counts and clinicopathological variables, progression-free survival and overall survival were examined. Between January 2010 and August 2010, 100 metastatic GC patients were enlisted. Among 100 patients, 5 or more CTCs (CTC-positive) were detected in 27 of 95 patients (28%). Even though the clinical characteristics of the CTC-positive and CTC-negative groups were not significantly different, the treatment response to cytotoxic chemotherapy in the CTC-positive group was significantly poorer (progressive disease: 23.4% vs. 60.0% in CTC-negative vs. CTC-positive group, respectively; p = 0.004). The median progression-free survival of the CTC-positive group was substantially shorter than that of the CTC-negative group (59 days vs. 141 days; p = 0.004). For overall survival, CTC-positive group had significantly shorter survival than CTC-negative group (median OS, 120 days vs. 220 days; p = 0.030). A multivariate Cox proportional hazards regression model showed that CTC positivity was an independent adverse factor for progression-free survival and overall survival. This study suggests CTCs are associated with poor response to chemotherapy in metastatic GC-patients.

Increased serum levels of interleukin-10 predict poor prognosis in extranodal natural killer/T-cell lymphoma patients receiving asparaginase-based chemotherapy.

There are currently no prognostic biomarkers for extranodal natural killer/T-cell lymphoma (ENKTL) patients receiving asparaginase-based chemotherapy. Interleukin-10 (IL-10) is a pleiotropic cytokine that is involved in the stimulation and suppression of immune responses and influences the prognosis of different subtypes of lymphoma. We retrospectively analyzed 98 newly diagnosed patients with ENKTL receiving asparaginase-based chemotherapy. Baseline serum IL-10 levels were tested with sandwich enzyme-linked immunosorbent assays. Patients with high IL-10 (≥12.28 pg/mL) at diagnosis tended to have more adverse clinical features. Patients with low IL-10 (<12.28 pg/mL) at diagnosis had better progression-free survival (PFS) (P>0.001) and overall survival (OS) (P<0.001). Multivariate analysis revealed that baseline serum IL-10 level ≥12.28 pg/mL, stage III/IV, elevated serum ferritin, and elevated serum Epstein–Barr virus DNA level at diagnosis were four adverse factors for PFS and OS. Based on these four independent prediction factors, we divided the patients into different subgroups as follows: group 1, no adverse factors; group 2, one factor; group 3, two factors; and group 4, three or four factors. Furthermore, significant differences in PFS and OS were found between the groups. Our results suggest that pretreatment serum IL-10 is a novel, powerful predictor of prognosis for ENKTL patients receiving asparaginase-based chemotherapy, which suggests a role for IL-10 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.

Prognostic factors for advanced‐stage human immunodeficiency virus‐associated classical Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine plus combined antiretroviral therapy: A multi‐institutional retrospective study

The treatment and outcomes of patients with human immunodeficiency virus (HIV)-associated Hodgkin lymphoma (HL) continue to evolve. The International Prognostic Score (IPS) is used to predict the survival of patients with advanced-stage HL, but it has not been validated in patients with HIV infection. This was a multi-institutional, retrospective study of 229 patients with HIV-associated, advanced-stage, classical HL who received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus combination antiretroviral therapy. Their clinical characteristics were presented descriptively, and multivariate analyses were performed to identify the factors that were predictive of response and prognostic of progression-free survival (PFS) and overall survival (OS). The overall and complete response rates to ABVD in patients with HIV-associated HL were 91% and 83%, respectively. After a median follow-up of 5 years, the 5-year PFS and OS rates were 69% and 78%, respectively. In multivariate analyses, there was a trend toward an IPS score >3 as an adverse factor for PFS (hazard ratio [HR], 1.49; P=.15) and OS (HR, 1.84; P=.06). A cluster of differentiation 4 (CD4)-positive (T-helper) cell count <200 cells/μL was associated independently with both PFS (HR, 2.60; P=.002) and OS (HR, 2.04; P=.04). The CD4-positive cell count was associated with an increased incidence of death from other causes (HR, 2.64; P=.04) but not with death from HL-related causes (HR, 1.55; P=.32). The current results indicate excellent response and survival rates in patients with HIV-associated, advanced-stage, classical HL who receive ABVD and combination antiretroviral therapy as well as the prognostic value of the CD4-positive cell count at the time of lymphoma diagnosis for PFS and OS.

Allogeneic Transplantation with Reduced-Intensity Conditioning for Hodgkin and non-Hodgkin Lymphoma: Importance of Histology for Outcome

Allogeneic stem cell transplantation (SCT) with reduced-intensity conditioning (RIC) has the potential to lead to long-term remissions for patients with lymphoma. However, the role of RIC SCT in the treatment of lymphoma is still unclear. Specifically, the relative benefit of RIC SCT across lymphoma histologies and the prognostic factors in this population are incompletely defined. We retrospectively analyzed the outcomes of 87 patients with advanced lymphoma who underwent RIC SCT at the Dana-Farber Cancer Institute over a 6-year period with a homogeneous conditioning regimen consisting of fludarabine and low-dose busulfan. Thirty-six patients had Hodgkin disease (HD) and 51 had non-Hodgkin lymphoma (NHL). Sixty-eight percent had undergone prior autologous transplantation. The 1-year cumulative incidence of nonrelapse mortality was 13%, and the 3-year cumulative incidence of progression was 49%. The incidence of grade 3-4 acute GVHD was 11%. The 2-year cumulative incidence of chronic GVHD was 68%, and its development was associated with a decreased risk of progression and an improved progression-free survival (PFS). Three-year overall survival (OS) was 56% for patients with HD, 81% for indolent NHL, 42% for aggressive NHL, and 40% for mantle cell lymphoma. The corresponding figures for 3-year PFS were 22%, 59%, 22%, and 30%, respectively. Multivariate analysis identified elevated pretransplantation lactate dehydrogenase (LDH) as an adverse factor for PFS, while indolent NHL histology was favorable. For OS, advanced age and elevated pretransplantation LDH were adverse factors, whereas indolent NHL histology was favorable. Low early donor chimerism was not predictive of poor outcome in univariate or multivariate analyses. Moreover, progression was not associated with loss of chimerism. These results emphasize the importance of lymphoma histology for patients undergoing RIC SCT, as well as the lack of relevance of donor chimerism for outcome in this patient population.

Non-Myeloablative Allogeneic Transplantation for Hodgkin's and Non-Hodgkin's Lymphoma: Evidence for a Graft-Versus-Lymphoma Effect and Relevance of Chimerism.

The role of non-myeloablative allogeneic stem cell transplantation (NST) in the treatment of patients with Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL) is still undefined. We report the outcomes of 87 patients with lymphoma who underwent NST at our institution. Thirty-six patients had HD and 51 had NHL (13 indolent NHL (indNHL), 23 aggressive NHL (aggNHL), and 15 mantle cell lymphoma (MCL)). Median age was 46 (18–64). Patients had received a median of 4 prior lines of therapy; 94% of the HD patients had received a previous autograft, as had 49% of NHL patients. 28% of patients were transplanted in CR, 49% in PR, and 23% with stable or progressive disease. The conditioning regimen consisted of IV busulfan (0.8 mg/kg/d × 4) and fludarabine (30 mg/m2/d × 4). Donors were matched related (38%), matched unrelated (56%), or mismatched (6%). Most patients received GVHD prophylaxis with a calcineurin inhibitor plus sirolimus or methotrexate. All patients engrafted. The 3-year cumulative incidence of non-relapse mortality (NRM) was 23%, and of relapse was 50%. The cumulative incidence of grade 2–4 acute GVHD was 16%, and the 2-year incidence of chronic GVHD was 68%. With a median follow-up of 21 months for survivors, the projected 3-year overall survival (OS) was 59% for patients with HD, 79% for indNHL, 42% for aggNHL, and 36% for MCL. The corresponding figures for 3-year progression-free survival (PFS) were 17% for HD, 59% for indNHL, 21% for aggNHL, and 30% for MCL. Figure Figure Multivariate analysis identified elevated pre-transplantation LDH and more than 4 prior lines of therapy as adverse factors for PFS, while indolent NHL histology was a favorable factor. In time-dependent multivariable models, grade 3–4 acute GVHD was associated with increased NRM and relapse, and decreased PFS and OS. Chronic GVHD was associated with a lower risk of relapse and improved PFS, without a significant effect on OS. The protective effect of chronic GVHD on relapse applied to all histologies except for aggNHL. Forty-five percent of relapsed patients (13 pts with HD and 5 with aggNHL) received donor lymphocyte infusion (DLI). The overall response rate (ORR) was 15% (2/13) for patients with HD, with both patients remaining progression-free at last follow-up; ORR was 40% (2/5) for patients with aggNHL, but responses were transient. For all patients, median chimerism at day 20–50 was 97% (range 46–100). Low early donor chimerism was not predictive of relapse, PFS, or OS in univariate or multivariate analyses. Moreover, relapse was not associated with loss of chimerism. Finally, chimerism at the time of DLI had no apparent bearing on its outcome. Conclusions: NST results in high PFS for indolent NHL. There is evidence of a graft-versus-lymphoma effect. Chimerism is not at any point predictive of relapse or of outcome. Future research could be aimed at increasing specific anti-lymphoma immune activity to harness GVL without increasing the incidence of GVHD.