Unrelated Donor Transplantation for Fanconi Anemia: Analysis of Prognostic Factors Impacting Engraftment and Survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 824-824 ◽  
Author(s):  
John E. Wagner ◽  
Mary Eapen ◽  
Richard E. Harris ◽  
Margaret L. MacMillan ◽  
Arlene D. Auerbach
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
T Cell ◽  
Fanconi Anemia ◽  
Blood Product ◽  
Complementation Group ◽  
Unrelated Donor ◽  
Neutrophil Recovery ◽  
Preparative Regimen ◽  
The Impact

While allogeneic transplantation is the only approach that can correct hematological complications of Fanconi anemia (FA), unrelated donor transplantation has been severely limited by graft rejection and regimen-related toxicity with resultant poor survival. Therefore we evaluated the impact of potential prognostic factors on hematopoietic recovery, graft-versus-host disease (GVHD) and overall survival in 98 recipients of unrelated donor transplantation, transplanted in 1990 to 2003. Median age at transplantation was 12 years (range 0.8 – 33). Of the 67 patients with known complementation group, 35 were in group A, 12 in group C and 7 in other groups and, 45 of 98 (46%) had diepoxybutane (DEB) T cell mosaicism. Sixty-nine percent had aplastic anemia prior to transplantation; 56% received prior androgen therapy and 24% received > 20 blood product transfusions. Fifty-four percent received cyclophosphamide and irradiation and, 46% received a fludarabine-containing preparative regimen (FLU). All patients received bone marrow grafts and 78% were matched at HLA A, B, (low resolution) and DRB1 or mismatched (22%) at a single locus. Seventy-one percent of grafts were T-cell depleted. In order to adjust for differences in follow up between recipients treated with and without FLU-containing preparative regimens (median 21 vs. 135 months; FLU was used exclusively after 1998), all patients were censored at 12 months for transplant-outcomes. Neutrophil recovery (>500/ul) was significantly less likely with non-FLU containing preparative regimens in patients with DEB mosaicism (cumulative incidence 52%, p<0.0001) than without DEB mosaicism (89%); however, neutrophil recovery was not influenced by DEB mosaicism with FLU containing preparatory regimens (94% and 93%). Similarly, platelet recovery (>20,000) was less likely with non-FLU containing preparatory regimens (19% vs. 76%, p<0.0001); favorable risk factors were absence of myelodysplasia/leukemia and < 20 blood product transfusions prior to transplantation. Acute and chronic GVHD were significantly lower in recipients of T-cell depleted grafts (17% and 18%, respectively) than recipients of non T cell depleted grafts (62% and 47%, respectively). Mortality was significantly higher with non-FLU containing preparative regimens (Relative Risk [RR] 3.24, 95% CI 1.86 – 5.66, p<0.0001), than with FLU containing preparative regimens. Corresponding probabilities of overall survival were 17% and 57%, respectively. Mortality was also significantly higher in patients who had received > 20 blood product transfusions (RR 2.10, 95% CI 1.16 – 3.76, p=0.01). Age, disease status at transplantation, HLA disparity, complementation group, DEB mosaicism or DEB sensitivity, and donor-recipient CMV status did not affect mortality. Based on these results significant practice changes should be considered: use of a FLU containing preparative regimen and transplantation prior to > 20 blood product transfusions.

scholarly journals Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia

Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 2256-2262 ◽  
Author(s):  
John E. Wagner ◽  
Mary Eapen ◽  
Margaret L. MacMillan ◽  
Richard E. Harris ◽  
Ricardo Pasquini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Fanconi Anemia ◽  
Marrow Transplantation ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Donor Bone Marrow ◽  
The Impact

AbstractBone marrow transplantation (BMT) is the only known cure for the hematologic manifestations of Fanconi anemia (FA). Potential benefits of unrelated donor BMT for FA, however, have been severely limited by graft rejection and treatment-related mortality with resultant poor survival. Therefore, we evaluated the impact of potential prognostic factors on hematopoietic recovery, graft-versus-host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs 69%; P = .02) and platelet (74% vs 23%; P < .001) recovery were higher after fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non–T-cell–depleted grafts. The day-100 mortality rate was significantly higher after nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs 24%, respectively; P < .001). Corresponding 3-year adjusted overall survival rates were 13% versus 52% (P < .001). In addition, mortality was higher in recipients who were older (> 10 years), who were cytomegalovirus (CMV) seropositive, and who received more than 20 blood product transfusions before BMT. Based on these results, significant practice changes are suggested: use of a fludarabine-containing conditioning regimen in the context of T-cell–depleted marrow allografts, and earlier referral for transplantation prior to excessive transfusions in patients with marrow failure.

scholarly journals High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning

2015 ◽  
Vol 33 (21) ◽  
pp. 2392-2398 ◽  
Author(s):  
Ran Reshef ◽  
Austin P. Huffman ◽  
Amy Gao ◽  
Marlise R. Luskin ◽  
Noelle V. Frey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Unrelated Donor ◽  
Cd8 Cells ◽  
Cd8 Cell ◽  
The Impact ◽  
Reduced Intensity

Purpose To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. Patients and Methods We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. Results Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 108 CD8 cells per kilogram optimally segregated patients receiving CD8hi and CD8lo grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8hi graft, whereas approximately half of younger donors provided CD8hi grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8lo doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8hi doses (P = .03), but not for recipients of younger unrelated donor CD8lo grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. Conclusion Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT.

Increased Disease Relapse in HLA-DPB1 Matched Recipients of Unrelated Donor Transplants Is Not Confined to Pairs Matched for the Other Five HLA loci.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 829-829
Author(s):  
Bronwen E. Shaw ◽  
Steven G.E. Marsh ◽  
Neema P. Mayor ◽  
J. Alejandro Madrigal
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
The Other ◽  
Unrelated Donor ◽  
Matched Pairs ◽  
Disease Relapse ◽  
Increased Risk ◽  
Risk Of Disease ◽  
The Impact ◽  
Hla Molecules

Abstract A number of studies, considering diverse populations of recipients of Unrelated Donor (UD) Haematopoietic Stem Cell Transplants (HSCT), have shown an impact of the matching status of HLA-DPB1 on transplantation complications and/or outcome. Most of these studies have been performed in pairs who are completely matched for the other five important HLA loci, 10/10 (HLA-A, -B, -C, -DRB1, -DQB1). This excludes any additive or confounding effects due to other HLA mismatches. However, it is also known that while strong linkage disequilibrium exists between the other five HLA loci, this does not extend to DP. It may therefore be possible to analyse DPB1 matching as an individual risk factor (irrespective of the matching status for the other HLA molecules). We have analysed the outcome in 423 mixed transplant pairs who have received an HSCT from an unrelated donor. The majority of transplant protocols included T cell depletion (TCD) with CAMPATH (>75%). All pairs had high resolution tissue typing performed for six HLA loci. Of the pairs, 282 were matched at 10/10 alleles and 141 had mismatches for one or more of 10/10 alleles. There was no association between matching for DPB1 and matching for the other HLA types. In the 282 HLA matched pairs, 29% were DPB1 matched, and in the 141 HLA mismatched pairs, 28% were matched for DPB1. We first analysed the impact of DPB1 matching in only those pairs who were matched for five HLA loci (N=282). The three year probability of relapse was 61% (median: 461 days). There was a highly significantly increase in disease relapse in DPB1 matched pairs (74%) as compared to those pairs with either one or two DPB1 mismatches (56%) (log rank, p=0.001). There was no difference in this effect as the number of DPB1 incompatibilities increased (i.e. one or two incompatibilities were equally protective, 56% versus 55% respectively, log rank p=0.959). This finding persisted in a multivariate analysis including factors known to be associated with disease relapse. We next analysed the impact of DPB1 matching on disease relapse in the group overall (N=423). There was a significantly increased risk of relapse in this cohort if DPB1 was matched (log rank; p=0.0001). This finding persisted when only the pairs with one or more mismatches for 10/10 alleles were considered (N=141) (log rank; p=0.031). When the cohort was divided according to disease subgroup, we found similar results in both CML and ALL - the risk of disease relapse when DPB1 is matched was significantly higher than when it was mismatched (log rank; p=0.0009 and p=0.013 respectively). Although there was no significant difference in the overall survival dependant on DPB1 matching in the group overall, in ALL DPB1 matched pairs had a significantly worse overall survival (log rank; p=0.025). Thus, in recipients of TCD UD HSCT, a match for DPB1 is associated with a significantly increased risk of disease relapse, irrespective of the matching status for the other HLA molecules. No other HLA locus had any impact on disease relapse. We speculate that this may indicate that DPB1 plays a different role within the immune system to the other HLA molecules. It is possible that DPB1 interacts with molecules besides T cells (such as NK cells) for which it may serve as a ligand. These effects may be more marked following transplants using CAMPATH, as many cell types are depleted, and thus the ratio of recovering cells is skewed in comparison to the situation which exists after a T cell replete transplant.

Treatment of Peripheral T-Cell Lymphoma (PTCL) with High-Dose Chemotherapy and Autologous Stem Cell Transplantation (ASCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4682-4682
Author(s):  
Min Kyoung Kim ◽  
Shin Kim ◽  
Seoung Sook Lee ◽  
Sun Jin Sym ◽  
Dae Ho Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
T Cell ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Cell Dose ◽  
Poor Outcome ◽  
The Impact

Abstract Objectives: Although CHOP-type chemotherapy has been the mainstay of therapy, outcome of PTCL has been uniformly disappointing. Despite the poor outcome after conventional chemotherapy, the impact of high-dose chemotherapy (HDCT) and ASCT is not well defined in these patients. The purpose of this study is to evaluate the efficacy of ASCT and the prognostic factors in PTCL with ASCT. Patients and Methods: We performed a retrospective analysis of 40 PTCL patients from the Asan Medical Center treated between January 1995 to December 2005 with HDCT and ASCT. Results: A total 40 patients were enrolled. Median age was 39 years (range 18–63). Twenty patients had PTCL-U, 10 extranodal NK/T cell lymphomas, 5 anaplastic large cell lymphomas, 3 angioimmunoblastic, one hepatosplenic γσ T cell lymphoma, and one disseminated mycosis fungoides. Disease status at transplant were CR1 in 3, CR2 or more in 8, partial remission in 25 (PR1 in 8 and PR2 in 17), and refractory in 4 patients.Three (7.5%) therapy-related mortalities occurred. A median follow-up of 16 months (range, 5 to 135 months) for surviving patients, the median overall survival (OS) was 11.5 months and the 1-year probability of survival was 41.5%. Ten patients (25%) were alive without evidence of disease. The median OS of 11 patients with CR at ASCT were not reached and of these, 7 patients (63.6%) were alive with CR. In multivariate analysis, CR status at HDT and BM involvement at ASCT was the most important prognostic factor for event free survival (P=0.032, P=0.031, respectively). A pretransplant IPI ≤1 and infused CD34+ cell dose ≥5×106/kg were the prognostic factors for an improved overall survival (P = 0.04 and P = 0.025, respectively). Conclusion: The results of HDT with ASCT for the patients with PTCL who did not achieve a CR to first line or salvage chemotherapy are not satisfactory. The patients who did not achieve CR at ASCT and patients with low infused CD34+cell dose, BM involvement or high IPI score at ASCT have poor outcome.

scholarly journals Impact of Different T Cell Depletion Protocols on Immune Reconstitution Following Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-44
Author(s):  
Amandine Pradier ◽  
Adrien Petitpas ◽  
Anne-Claire Mamez ◽  
Federica Giannotti ◽  
Sarah Morin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Reconstitution ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
T Cell Depletion ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
The Impact

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic modality for a variety of hematological malignancies and congenital disorders. One of the major complications of the procedure is graft-versus-host-disease (GVHD) initiated by T cells co-administered with the graft. Removal of donor T cells from the graft is a widely employed and effective strategy to prevent GVHD, although its impact on post-transplant immune reconstitution might significantly affect anti-tumor and anti-infectious responses. Several approaches of T cell depletion (TCD) exist, including in vivo depletion using anti-thymocyte globulin (ATG) and/or post-transplant cyclophosphamide (PTCy) as well as in vitro manipulation of the graft. In this work, we analyzed the impact of different T cell depletion strategies on immune reconstitution after allogeneic HSCT. Methods We retrospectively analysed data from 168 patients transplanted between 2015 and 2019 at Geneva University Hospitals. In our center, several methods for TCD are being used, alone or in combination: 1) In vivo T cell depletion using ATG (ATG-Thymoglobulin 7.5 mg/kg or ATG-Fresenius 25 mg/kg); 2) in vitro partial T cell depletion (pTCD) of the graft obtained through in vitro incubation with alemtuzumab (Campath [Genzyme Corporation, Cambridge, MA]), washed before infusion and administered at day 0, followed on day +1 by an add-back of unmanipulated grafts containing about 100 × 106/kg donor T cells. The procedure is followed by donor lymphocyte infusions at incremental doses starting with 1 × 106 CD3/kg at 3 months to all patients who had received pTCD grafts with RIC in the absence of GVHD; 3) post-transplant cyclophosphamide (PTCy; 50 mg/kg) on days 3 and 4 post-HSCT. Absolute counts of CD3, CD4, CD8, CD19 and NK cells measured by flow cytometry during the first year after allogeneic HSCT were analyzed. Measures obtained from patients with mixed donor chimerism or after therapeutic DLI were excluded from the analysis. Cell numbers during time were compared using mixed-effects linear models depending on the TCD. Multivariable analysis was performed taking into account the impact of clinical factors differing between patients groups (patient's age, donor type and conditioning). Results ATG was administered to 77 (46%) patients, 15 (9%) patients received a pTCD graft and 26 (15%) patients received a combination of both ATG and pTCD graft. 24 (14%) patients were treated with PTCy and 26 (15%) patients received a T replete graft. 60% of patients had a reduced intensity conditioning (RIC). 48 (29%) patients received grafts from a sibling identical donor, 94 (56%) from a matched unrelated donor, 13 (8%) from mismatched unrelated donor and 13 (8%) received haploidentical grafts. TCD protocols had no significant impact on CD3 or CD8 T cell reconstitution during the first year post-HSCT (Figure 1). Conversely, CD4 T cells recovery was affected by the ATG/pTCD combination (coefficient ± SE: -67±28, p=0.019) when compared to the T cell replete group (Figure 1). Analysis of data censored for acute or chronic GVHD requiring treatment or relapse revealed a delay of CD4 T cell reconstitution in the ATG and/or pTCD treated groups on (ATG:-79±27, p=0.004; pTCD:-100±43, p=0.022; ATG/pTCD:-110±33, p&lt;0.001). Interestingly, pTCD alone or in combination with ATG resulted in a better reconstitution of NK cells compared to T replete group (pTCD: 152±45, p&lt;0.001; ATG/pTCD: 94±36, p=0.009; Figure 1). A similar effect of pTCD was also observed for B cells (pTCD: 170±48, p&lt;.001; ATG/pTCD: 127±38, p&lt;.001). The effect of pTCD on NK was confirmed when data were censored for GVHD and relapse (pTCD: 132±60, p=0.028; ATG/pTCD: 106±47, p=0.023) while only ATG/pTCD retained a significant impact on B cells (102±49, p=0.037). The use of PTCy did not affect T, NK or B cell reconstitution when compared to the T cell replete group. Conclusion Our results indicate that all TCD protocols with the only exception of PTCy are associated with a delayed recovery of CD4 T cells whereas pTCD of the graft, alone or in combination with ATG, significantly improves NK and B cell reconstitution. Figure 1 Disclosures No relevant conflicts of interest to declare.

Prognostic factors and the impact of frontline therapy in peripheral T-cell lymphoma: 10 years of ‘real-world’ experience from Western Australia

2019 ◽  
Vol 60 (14) ◽  
pp. 3417-3425
Author(s):  
James A. Kuzich ◽  
Andrew P. Hutchison ◽  
Kenneth J. C. Lim ◽  
Portia Smallbone ◽  
Kate Denning ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
T Cell ◽  
Western Australia ◽  
Real World ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Frontline Therapy ◽  
The Impact

scholarly journals Prognostic factors for pulmonary metastasectomy in malignant melanoma: size matters

2019 ◽  
Vol 56 (6) ◽  
pp. 1104-1109 ◽  
Author(s):  
Jan Viehof ◽  
Elisabeth Livingstone ◽  
Elena Loscha ◽  
Paul Stockhammer ◽  
Agnes Bankfalvi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Malignant Melanoma ◽  
Treatment Options ◽  
Pulmonary Metastasectomy ◽  
Long Term Outcome ◽  
Female Patients ◽  
Novel Treatment ◽  
The Impact

AbstractOBJECTIVESPulmonary metastasectomy for malignant melanoma requires an individualized therapeutic decision. Due to recently developed novel treatment options, the prognosis of patients with melanoma has improved significantly. Validated prognostic factors that identify patients who are most likely to benefit from metastasectomy are urgently needed.METHODSWe retrospectively reviewed all consecutive patients with melanoma undergoing complete pulmonary metastasectomy between January 2010 and December 2016. The impact of age, sex, extrapulmonary metastases, preoperative systemic therapy, number of metastases, laterality and largest diameter of metastasis on survival after metastasectomy was analysed.RESULTSA total of 29 male and 32 female patients were included in the study. The median follow-up time was 25.6 months. The mean number of resected metastases was 1.7 ± 1.1 (range 1–5). Ten patients had repetitive pulmonary metastasectomies. The median survival time was 31.3 months with a 2-year survival rate of 54%. Bilateral metastases or multiple nodules were not associated with a significantly decreased overall survival rate after metastasectomy. Shorter overall survival times were observed in male patients [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.42–5.92; P = 0.0035] and in patients with nodules larger than 2 cm (HR 3.18, 95% CI 1.45–6.98; P = 0.004). In multivariable analysis, both gender and tumour size remained significant independent prognostic factors.CONCLUSIONSExcellent overall survival rates after pulmonary metastasectomy for melanoma metastases were observed in patients with a metastatic diameter less than 2 cm and in female patients. In view of improved long-term outcome due to novel treatment options, the selection of patients for pulmonary metastasectomy based on prognostic factors will become increasingly important.

scholarly journals OS1.6 Peripheral blood immune profiles at first recurrence of IDH wild type glioblastoma after standard chemoradiotherapy predict overall survival: secondary analyses of the phase II DIRECTOR trial

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii6-iii7
Author(s):  
H Wirsching ◽  
E Terksikh ◽  
S Manuela ◽  
K Carsten ◽  
R Patrick ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Prognostic Factors ◽  
T Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Cd4 T Cell ◽  
Cox Models ◽  
First Recurrence ◽  
Cell Fractions

Abstract BACKGROUND Isocitrate dehydrogenase (IDH) wildtype glioblastoma is associated with distinctive peripheral blood immune cell profiles that evolve under first line chemoirradiation with temozolomide. Whether peripheral blood immune cell profiles at recurrence are associated with survival of IDH wildtype glioblastoma has not been studied in detail. PATIENTS AND METHODS Peripheral blood mononuclear cells (PBMC) of 21 healthy donors and of 52 clinically well-annotated patients with IDH wildtype glioblastoma were analyzed by 11-color flow cytometry at 1st recurrence after standard chemoirradiation with temozolomide and at 2nd recurrence after dose-intensified temozolomide re-challenge. Patients were treated within the randomized phase II trial DIRECTOR, which explored the efficacy of dose-intensified temozolomide at first recurrence of glioblastoma. Patients were classified based on unsupervised analyses of PBMC profiles at 1stand 2ndrecurrence. Associations with survival were explored in multivariate Cox models controlling for established prognostic and predictive factors. RESULTS At 1strecurrence, two patient clusters were identified which differed in CD4+ T-cell fractions, but not with respect to CD8+ T-cells, CD4+;CD25+;FoxP3+ regulatory T-cells, B-cells or monocytes. The composition of CD4+, CD8+ or regulatory T-cell fractions was similar in both clusters. All control samples clustered with the CD4high cluster. Patients in both clusters did not differ by established prognostic factors, including age, O6-methylguanine-DNA-methyl-transferase (MGMT) gene promoter methylation, tumor volume, Karfnosky performance score or steroid use. Progression-free survival was similar (CD4high vsCD4low 2.1 vs 2.4 months, p=0.19), whereas post-recurrence overall survival was longer among the CD4highcluster (12.7 vs 8.7 months, p= 0.004). At 2nd recurrence, monocyte fractions increased, whereas memory CD4+ T-cell fractions decreased. Unsupervised segregation of patients by CD4+ subpopulations yielded two clusters characterized by the abundance of memory T-cell fractions and higher memory CD4+ fractions were associated with longer overall survival at 2nd recurrence (p=0.004). The reported prognostic associations were retained in multivariate Cox models controlling for established prognostic factors. CONCLUSION We conclude that temozolomide-associated memory CD4+ T-cell depletion may have deteriorating effects on the survival of glioblastoma patients.

scholarly journals Meta-analysis of prognostic factors of overall survival in patients undergoing oesophagectomy for oesophageal cancer

2020 ◽  
Vol 33 (11) ◽  
Author(s):  
Sivesh K Kamarajah ◽  
Ella J Marson ◽  
Dengyi Zhou ◽  
Freddie Wyn-Griffiths ◽  
Aaron Lin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Oesophageal Cancer ◽  
Meta Analysis ◽  
Staging System ◽  
Tumor Grade ◽  
Pooled Analysis ◽  
Prognostic Models ◽  
Biological Variables ◽  
The Impact

ABSTRACT Introduction Currently, the American Joint Commission on Cancer (AJCC) staging system is used for prognostication for oesophageal cancer. However, several prognostically important factors have been reported but not incorporated. This meta-analysis aimed to characterize the impact of preoperative, operative, and oncological factors on the prognosis of patients undergoing curative resection for oesophageal cancer. Methods This systematic review was performed according to PRISMA guidelines and eligible studies were identified through a search of PubMed, Scopus, and Cochrane CENTRAL databases up to 31 December 2018. A meta-analysis was conducted with the use of random-effects modeling to determine pooled univariable hazard ratios (HRs). The study was prospectively registered with the PROSPERO database (Registration: CRD42018157966). Results One-hundred and seventy-one articles including 73,629 patients were assessed quantitatively. Of the 122 factors associated with survival, 39 were significant on pooled analysis. Of these. the strongly associated prognostic factors were ‘pathological’ T stage (HR: 2.07, CI95%: 1.77–2.43, P &lt; 0.001), ‘pathological’ N stage (HR: 2.24, CI95%: 1.95–2.59, P &lt; 0.001), perineural invasion (HR: 1.54, CI95%: 1.36–1.74, P &lt; 0.001), circumferential resection margin (HR: 2.17, CI95%: 1.82–2.59, P &lt; 0.001), poor tumor grade (HR: 1.53, CI95%: 1.34–1.74, P &lt; 0.001), and high neutrophil:lymphocyte ratio (HR: 1.47, CI95%: 1.30–1.66, P &lt; 0.001). Conclusion Several tumor biological variables not included in the AJCC 8th edition classification can impact on overall survival. Incorporation and validation of these factors into prognostic models and next edition of the AJCC system will enable personalized approach to prognostication and treatment.

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