scholarly journals Azacitidine Improves Outcome in Patients with MDS and AML with High Risk Cytogenetics - a Single Center Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5529-5529
Author(s):  
Vidhya Murthy ◽  
Nilupulee Kapuge ◽  
Charalampos Kartsios ◽  
Joanne Ewing ◽  
Evgenia Xenou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Platelet Count ◽  
High Risk ◽  
Neutrophil Count ◽  
Complex Karyotype ◽  
Free Survival ◽  
Educational Meeting ◽  
Transfusion Independence ◽  
Travel Grant

Abstract Azacitidine is a novel hypomethylating agent shown to improve leukaemia free survival and overall survival in comparison with other modalities of treatment in MDS and AML patients. There is proven reduction in transfusion requirements by improvement in haematological parameters with continuous azacitidine use. However azacitidine benefit in high risk cytogenetics group is unclear. Recent retrospective study from GESMD and GFM registries showed that Azacitidine improves outcome in higher‐risk MDS patients with chromosome 7 abnormalities. Here we report our experience in high risk cytogenetics group including complex karyotype. Methodology:- We retrospectively reviewed patients with MDS and AML who received Azacitidine at the Heart of England NHS Foundation Trust from April 2012- January 2018. Patient's demographic data, disease characteristics, treatment, outcome and follow up data were obtained and all patients were included irrespective of the number of the cycles. Results 57 patients were included in the analysis. Median age of treatment was 73.9 years. Median number of cycles was 6 (range from 1 to 43). There were 68% of MDS patients, 22.8% of AML and 8.8% of CMML2 patients in the cohort .Varying degree of performance stage was noted including ECOG 0,1 and 2 at 40.4%,43.9% and 7.7% respectively. 9 patients had monosomy 7 and 11 patients had complex karyotype (3/>3). 42.1% had high risk cytogenetics. At presentation, median Hb was 9g/dl, Neutrophil count was 0.7x109/l and platelet count was 41x109/l. Median bone marrow blast percentage was10% and median RIPSS score was 6.5. Causes of death were mainly disease progression and sepsis. 42.2% died due to disease progression and 35.1% died due to sepsis. Overall survival was not affected by age, Bone marrow median blast percentage and median neutrophil count, however, survival was affected by presenting peripheral blast percentage, cytogenetic risk group and was statistically significant (P<0.05) Overall, median progression free survival (PFS) was 19monts while median overall survival (OS) was 12 months. There was no statistically significant PFS or OS difference for patients who had varying performance stage. High risk cytogenetics group: Among high risk cytogenetics group, 21% Patients had red cell transfusion independence at 6 months, 28% had an improvement in the neutrophil count to >1x10^9/L at 6 months. 25% patients had doubling of platelet count at 3 months leading to platelet independence and 17.8% maintained platelet transfusion independence. A significant difference was noted in the group of who had high risk cytogenetic versus other cytogenetic risks with PFS of 15 and 29 months respectively, OS of 8 months and 15 months respectively. with high risk cytogenetics still had a PFS advantage with treatment. Conclusion Azacidine therapy has benefited for the patients who had advanced age AML CMML and MDS who has non high risk cytogenetic based on IPSS-R risk categorization. However, the group of patients with high risk cytogenetic considered historically very poor survival had considerable PFS and OS benefitting treatment rather than best supportive care. Figure. Figure. Disclosures Murthy: celgene: Consultancy, Other: Travel grant for educational meeting; Abbview: Other: Travel grant for Educational meeting. Kartsios:Bayer: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Speakers Bureau; Boehringer Inglelheim: Consultancy, Honoraria, Speakers Bureau. Nikolousis:Celgene: Consultancy, Other: Travel grant for educational meetings.

The Level of AKT Phosphorylation on Threonine 308 but Not on Serine 473 Is Associated with High-Risk Cytogenetics and Predicts Poor Overall Survival in Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1503-1503
Author(s):  
Nathalie Gallay ◽  
Cédric Dos Santos ◽  
Lise Cuzin ◽  
Marina Bousquet ◽  
Violaine Simonnet Gouy ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Group ◽  
Mutation Screening ◽  
Complete Analysis ◽  
Dependent Manner ◽  
Complex Karyotype ◽  
Free Survival ◽  
Akt Phosphorylation ◽  
Pp2a Activity

Abstract The PI3K/Akt pathway is an important signaling pathway governing cell survival, proliferation and drug resistance in AML. However, the prognosis impact of Akt phosphorylation in AML has yielded some controversies as far as the phosphorylation on Ser473 is concerned. Because full activation of Akt requires phosphorylation on both Thr308 and Ser473, the assessment of these two sites would allow a more complete analysis of Akt activation in AML cells. We have studied the level of phosphorylation on both sites in primary AML samples by flow cytometry. We retrospectively assessed samples from 58 AML patients treated between 12/2000 and 02/2005. The clinical characteristics were: median age, 46.5 y (15–61); sex ratio (M/F) 1.24; FAB, 1 M0, 29 M1/M2, 25 M4/M5, 1 M6, 2 unclassified; median WBC, 33.4 G/L (1.2–225); Hb, 9.2 g/dL (5–13.5); platelets, 48 G/L (6–328); % marrow blasts, 78 (20–97); cytogenetic risk group (favorable, 28%; intermediate, 31%; unfavorable, 19%); FLT3-ITD, 10/54 (19%). The complete response rate after induction chemotherapy (anthracyclines + ara-C) was 83%. Patients in CR1 were referred to consolidation chemotherapy, autologous or allogeneic stem-cell transplantion according to the cytogenetic risk. The global overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were of 22.1, 14.1, and 15.6 months, respectively. The levels of Akt phosphorylation (Thr308 and Ser473) were evaluated on pretreatment marrow samples and expressed by the ratio between mean fluorescence intensity of the stained AML sample and non-relevant IgG control (rMFI). The values of both Thr308 and Ser473 represented a continuum ranging from 0.3 to 5.6 and 0.4 to 2.87, respectively. The median level of phosphorylation was 2.3 (±0.89) and 1.3 (±0.27) for Thr308 and Ser473, respectively. There were no significant correlations between age, gender, FAB, WBC, FLT3-ITD and Akt phosphorylation. However, the level of phosphorylation on Thr308 but not on Ser473 was significantly correlated with the cytogenetic risk group. Indeed, the median rMFIs on Thr308 were 1.95 (± 0.37); 2.2 (±1) and 3.1 (±0.49) for favorable, intermediate and unfavorable karyotype, respectively (p=0.0069). In univariate analysis, unfavorable karyotype, FLT3-ITD and Thr308high correlated with poor OS, EFS, and RFS. Thr308high patients (&gt; median value) had significantly shorter OS (11 vs 47 months; p=0.01), EFS (9 vs 26 months; p=0.005) and RFS (10 months vs not reached; p=0.02) than Thr308low patients. In the Cox model for multivariate analysis, only the cytogenetic risk independently predicted worse RFS, EFS and OS. Neither mutation screening for AKT1 E17K in an independant series of 148 AML cases nor changes in the level of PTEN expression and phosphorylation could explain the increased phosphorylation of Thr308 in high-risk cytogenetics AML cells. However, we found a statistically significant correlation between protein phosphatase 2A (PP2A) activity and complex karyotypes. Indeed, PP2A activity was markedly reduced by 40% in complex karyotypes compared with normal karyotypes. To specifically assess the role of Akt in the survival and proliferation of complex karyotype AML cells, we used the allosteric Akt kinase inhibitor targeting Akt1 and Akt2 (Akt-i). Akt-i inhibited the phosphorylation of Akt on both sites in these cells. Akt-i inhibited the clonogenic activity of AML cells from normal and complex karyotype samples in a dose-dependent manner, but this effect was significantly more potent in complex than in normal karyotype samples. After 24 h incubation with 10 μM Akt-i, features of apoptosis were detected by Annexin V staining (25% ±3,38 in treated vs 14% in untreated cells). Moreover, Akt-i enhanced the toxicity of daunorubicin (37% ±2,9, Akt-i+dnr vs 25% ±3,5, dnr). We also detected Akt phosphorylation in the immature leukemic compartment (CD34+ CD38− CD123+). Accordingly, Akt-i also induced apoptosis and enhanced dnr activity in CD34+ CD38− CD123+ cells from complex karyotype samples. This study shows that AML cells with complex karyotype display high level of phosphorylation of AktThr308 and suggests that this anti-apoptotic pathway may represent a valuable therapeutic target. Thus, it will be important to determine in clinical trials if this aberrant activation of Akt sensitizes AML cells to PI3K/Akt inhibitors specifically in this subgroup of very high-risk patients.

scholarly journals Predictive Factors for Complete Remission and Survival in AML Patients Failing to Achieve Adequate Bone Marrow Day 14 Blast Eradication

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1464-1464
Author(s):  
Rafee Talukder ◽  
Sarvari Venkata Yellapragada ◽  
Hussein Hamad ◽  
Gustavo A. Rivero
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
High Risk ◽  
Complete Remission ◽  
Induction Therapy ◽  
Research Funding ◽  
Complex Karyotype ◽  
Early Assessment ◽  
Secondary Aml ◽  
Impact On Survival

Abstract Introduction: Complete remission (CR) is an important endpoint after cytarabine plus anthracycline [7+3] induction therapy in Acute Myelogenous Leukemia (AML). Even though CR is observed in about 50-90% of unselected European Leukemia Network 2017 (ELN-2017) patients (pt), factors such as age >65 years, complex karyotype, and adverse mutations (RUNX1, ASLX1, TP53, FLT3 ITD high, KMT2A, secondary AML), leads to inadequate blast eradication. Early response to induction is a predictor of subsequent complete remission (CR). Bone marrow day 14 [D14] inform pt with early inadequate leukemia eradication [blast >10%] who are suitable for re-induction, a strategy that seeks to facilitate conversion to CR or CR with incomplete hematologic recovery (CRi), secure potential allogenic transplantation and reproduce superior outcomes. In this study, we investigated the clinical outcome of an unselected ELN-2017 AML cohort with inadequate D14 marrow response. From the subgroup of patients exhibiting sub-optimal response (SOR), we examined the odds and predictors for subsequent achievement of CR/CRi for those patients who did not receiving immediate re-induction therapy. Additionally, we evaluated the effect of subsequent CR/CRi achievement on survival. Methods: With prior IRB approval, 160 AML pt diagnosed with AML from 1995 to 2017 within Baylor College of Medicine institutions were evaluated. Kaplan-Meier method was used to estimate overall survival (OS) among pt achieving D14 <> 10% blast in an unselected ELN-2017 AML cohort and pt exhibiting >10% blast in D14 marrow with and without CR/CRi. Logistic and cox regression analysis in SOR pt [1] attaining subsequent CR/CRi and [2] OS, respectively, was performed to investigate multiple independent variables with predictive value for the 2 above outcomes. Results: 68/160 (42.5%) of pt had available D14 [early assessment] and sequential day 30 marrow for CR/CRi evaluation. Among 68 unselected ELN-2017 AML pt with D14 marrow for CR/CRi assessment, 42/68 (61.7%) and 26/68 (38.2%) had D14 marrow blasts < and > 10%. Median age was 57 y (range 27-73) and 59 y (range 24-89), respectively, p= 0.74. OS was 459 d vs 169 d in pt with D14 marrow <10% and >10%, at day 14 (p=0.001 95% CI 0.2-0.9) [Fig 1A]. CR/CRi was observed in 36/42 (90%) and 10/26 (38.7%) of pt with D14 marrow <10% vs >10%, respectively, p=0.0005. After controlling for traditional high-risk factors including WBC, age, platelet count, RDW, de novo v secondary AML, only ELN-2017 classification [fav vs unfav and intermediate vs unfav, p= 0.0026 and p=0.01] retained impact on survival. In pt with SOR, we performed second analysis to investigate survival among pt with and without subsequent CR/CRi achievement who did not receive re-induction [Fig 1B]. 16/26 (62.5%) of pt with SOR failed to achieved CR/CRi. OS was 333 d vs 109 d for pt with CR/CRi vs those without CR/CRi [p=0.002, 95% CI 2.6-3.4]. Logistic regression identified in pt with CR/CRi vs those without CR/CRi that: [a] age [63.1 vs 43.6 y-p=0.001]; [b] lower platelet count [47.1 vs 83.1 K/uL-p=0.03]; [c] higher absolute monocyte count (AMC) [3.7 vs 0.41 K/uL-p=0.04]; [d] increased RDW [18.3 vs 14.7-p=0.004] and [e] high BMI [31 vs 24.1-p=0.0003] were significantly associated with failure to achieve CR/CRi. Typical complex karyotype and initial marrow blast % were not associated with subsequent CR/CRi achievement. However, in pt with SOR, lack of high-risk mutations [P53, RUNX, FLT3-ITD, U2AF1] was significant associated with CR/CRi, [40% v 62.5%, p= 0.0004]. Cox proportional regression model showed significant impact on survival for high-risk mutations and higher BMI in survival. Conclusion: In our retrospective study, despite 38.7% of patients with detectable D14 residual leukemia achieved CR/CRi without re-induction, failure to attain CR/CRi was frequently observed after SOR. Advanced age, lower platelet count, higher AMC, RDW and BMI predict failure to achieve CR/CRi status in patients exhibiting initial SOR. Lack of high-risk mutation was a strong predictor for CR/CRi achievement. Our study is novel by suggesting that a combination of pre-induction and "early post-induction" variables facilitate recognition of high-risk AML subgroups requiring re-induction or alternative novel therapy via clinical trials. Disclosures Yellapragada: Takeda: Research Funding; Novartis: Employment; Celgene: Research Funding.

scholarly journals Next-Generation Sequencing in Myelodysplastic Syndromes: Prognostic Interaction Between Adverse Mutations and IPSS-R

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1986-1986
Author(s):  
Naseema Gangat ◽  
Terra L. Lasho ◽  
Lyla Saeed ◽  
Mythri Mudireddy ◽  
Mrinal M Patnaik ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Overall Survival ◽  
Platelet Count ◽  
Lower Risk ◽  
Univariate Analysis ◽  
Bone Marrow Blast ◽  
Free Survival ◽  
Clinical Correlates ◽  
Generation Sequencing

Abstract Background In a seminal report (NEJM 2011;30:2496), ASXL1, TP53, EZH2, ETV6 and RUNX1 mutations in myelodysplastic syndromes (MDS) were shown to carry an adverse prognostic impact that was independent of the international prognostic scoring system (IPSS) (Blood 1997;89:2079). Two recent studies (Leukemia20 May 2016; doi: 10.1038/leu.2016.138; Leukemia. 2014;28:241) have proposed mutation-enhanced prognostic models that include the revised IPSS (IPSS-R) (Blood 2012;120:2454 ). In the current study, we applied targeted next generation sequencing (NGS) in order to examine the prognostic interaction between adverse mutations and IPSS-R. Methods The study population was recruited from our institutional database of patients with primary MDS, based on availability of archived DNA from the time of diagnosis. The diagnosis of MDS and leukemic transformation (LT) was made according to WHO criteria (Blood. 2009;114:937). Targeted capture assays were carried out, on bone marrow DNA specimens, for the following genes: TET2, DNMT3A, IDH1, IDH2, ASXL1, EZH2, SUZ12, SRSF2, SF3B1, ZRSR2, U2AF1, PTPN11, Tp53, SH2B3, RUNX1, CBL, NRAS, JAK2, CSF3R, FLT3, KIT, CALR, MPL, NPM1, CEBPA, IKZF, and SETBP1.Specific variants were deemed as mutations if they are associated with a hematologic malignancy (as identified by COSMIC database), or if they have not been associated with a dbSNP. Results Patient characteristics and type and number of mutations: 179 patients were evaluated (median age 73 years; 68% males). IPSS-R risk distribution was 11% very high, 18% high, 16% intermediate, 39% low and 16% very low. At least one mutation was seen in 139 (78%) patients including 17% with one mutation, 29% with 2, 20% with 3, 10% with four, 2% with 5 and one patient with 6 mutations. The most frequent mutations were ASXL1 (30%), SF3B1 (20%), TET2 (17%), U2AF1 (16%) and SRSF2 (16%). Mutation clusters and clinical correlates: ASXL1 mutations were associated with the absence of SF3B1 (p=0.007), U2AF1 (p=0.01) and SRSF2 (p=0.003) mutations; SF3B1 with absence of U2AF1 (p=0.004) and SRSF2 (p=0.004) mutations; and U2AF1 with absence of SRSF2 mutations (p=0.01). Clinical correlates of ASXL1 mutations included older age, lower hemoglobin, and lower risk karyotype; SF3B1 with higher leukocyte count, higher platelet count, lower bone marrow blast percentage and lower risk karyotype; TET2 with older age and higher hemoglobin. Univariate overall and leukemia-free survival analysis before and after adjusting for IPSS-R: In univariate analysis, ASXL1, RUNX1 and TP53 mutations adversely and SF3B1 favorably affected survival; only ASXL1 mutations retained significance when analysis was adjusted for IPSS-R (HR 1.5, 95% CI 1.0-2.1; p=0.03). For leukemia-free survival, univariate analysis identified SRSF2, which was near-significant for overall survival (p=0.06), and RUNX1 mutations as adverse and SF3B1 mutations as favorable risk factors; SRSF2 (HR 4.1, 95% CI 1.6-10.2) and SF3B1-unmutated (HR 5.9, 95% CI 1.1-31.5) retained their significance when adjusted for IPSS-R. A borderline significance (p=0.07) indicating inferior survival for patients with three or more mutations was fully accounted for by the significant (P<0.0001) association between the presence of ASXL1 mutations and higher number of mutations. Multivariable analysis with individual IPSS-R variables: When the five IPSS-R variables (hemoglobin, platelets, absolute neutrophil count, bone marrow blast percentage and karyotype) were analyzed (both as continuous and IPSS-R-defined categorical variables) with each one of the aforementioned mutations with significant effect on overall or leukemia-free survival, only ASXL1 retained its significance for overall survival (HR 1.6, 95% CI 1.1-2.3) and SRSF2 (HR 5.2, 95% CI 2.1-13.3) for leukemia-free survival. Other IPSS-R variables that retained their significance for survival, in the presence of ASXL1 mutation status as a covariate, included hemoglobin level, platelet count and karyotype. Conclusions: In our cohort of 179 molecularly-annotated patients with newly-diagnosed primary MDS, ASXL1 and SRSF2 mutations were identified as IPSS-R-independent risk factors for overall and leukemia-free survival, respectively. The current study also suggests the need to re-evaluate currently established risk factors, in the context of prognostically-relevant molecular information. Disclosures No relevant conflicts of interest to declare.

scholarly journals IMMU-08. MODELING UPFRONT GLIOBLASTOMA SURGICAL RESECTION AND STEROID USE REVEALS IMMUNOSUPPRESSIVE CHANGES AND SUGGESTS THAT PERIPHERAL LYMPHOCYTE COUNTS ARE ASSOCIATED WITH TUMOR VOLUME AND PROGNOSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii106-ii106
Author(s):  
Balint Otvos ◽  
Tyler Alban ◽  
Matthew Grabowski ◽  
Defne Bayik ◽  
Robert Winkelman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Surgical Resection ◽  
Cd8 T Cells ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Peripheral Lymphocyte ◽  
Steroid Use ◽  
Free Survival ◽  
Steroid Administration

Abstract Glioblastoma (GBM) and its treatment produces systemic immunosuppression, which is being targeted by immunotherapies. However, it remains unclear how surgical resection and steroids specifically in GBM alter the immune system. To further explore this issue, immunocompetent C57Bl/6 mice were intracranially inoculated with syngeneic glioma cells (GL261 and CT-2A) and growth of tumors was evaluated by MRI. Host immune cell populations were analyzed during surgical resection and steroid administration. Mice with surgically resected tumors had a longer median survival compared to mice subjected to tumor biopsies, and had increased bone marrow sequestration of both CD4 and CD8 T cells with corresponding decreased blood lymphocytes. Furthermore, physiologic doses of dexamethasone administered perioperatively decreased tumor edema, but increased the number and proliferative capacity of both marrow and circulating MDSCs while generating no survival benefit. Independent of therapy or dexamethasone, intracranial tumor volume correlated linearly with decreased CD4 and CD8 T cells in peripheral blood, and increased T cell sequestration within the bone marrow. We validated these parameters in steroid-naïve newly diagnosed GBM patients and observed decreased lymphocytes correlated linearly with increased tumor volume. When initial lymphocyte counts in both steroid-naïve and steroid-administered patients were used in univariate and multivariate models predicting progression-free survival and overall survival, decreased initial lymphocyte counts were an independent predictor of decreased progression free survival and decreased overall survival, with steroid use and initial tumor size falling out of significance during stepwise selection. Taken together, tumor volume is linearly correlated with marrow sequestration of lymphoid cells, but both surgery and steroid administration further suppress active immune responses along lymphoid and myeloid lineages. Furthermore, decreasing peripheral lymphocyte counts at diagnosis of GBM indicate an immune system less able to mount responses to the tumor and portent a worse progression free and overall survival.

Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Saudi Arabia ◽  
Neutrophil Count ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
P Value ◽  
Second Line ◽  
First Line ◽  
Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

Treatment of Pulmonary Metastases in Children With Stage IV Nephroblastoma With Risk-Based Use of Pulmonary Radiotherapy

2012 ◽  
Vol 30 (28) ◽  
pp. 3533-3539 ◽  
Author(s):  
Arnauld Verschuur ◽  
Harm Van Tinteren ◽  
Norbert Graf ◽  
Christophe Bergeron ◽  
Bengt Sandstedt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
High Risk ◽  
Pulmonary Metastases ◽  
Stage Iv ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Purpose The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients. Patients and Methods Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory. Results Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001). Conclusion Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.

Postoperative PET/CT for detection of early recurrence (ER) after surgery for squamous cell carcinomas (SCC) of the oral cavity (OC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6060-6060
Author(s):  
Yao Yu ◽  
Heiko Schöder ◽  
Jung Kang ◽  
Sean Matthew McBride ◽  
C. Jillian Tsai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
High Risk ◽  
Postoperative Radiotherapy ◽  
Prospective Trial ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Risk Groups ◽  
Free Survival ◽  
Pet Ct

6060 Background: Patients with ER after surgery and prior to postoperative radiation (RT) for SCC of the OC have aggressive biology and poor prognosis. After the introduction of a PET/CT simulator in our department, we incorporated post-operative PET/CT as part of RT planning. We hypothesized PET/CT would improve detection of macroscopic disease before postoperative RT. Methods: We reviewed the medical records of patients treated with postoperative radiotherapy between 2005 and 2019 for OC SCC. Clinicopathologic risk factors were recorded. Intermediate risk factors (IRFs) included pT3-4 disease, nodal disease, perineural invasion (PNI), lymphovascular invasion (LVI), and close ( < 5mm) surgical margins (SM); extranodal extension (ENE) and positive SM were considered high-risk factors (HRF). Patients were stratified into risk groups based upon the number and type of risk factors: 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF. Patients were considered to have ER if they had biopsy confirmed recurrence, or if the imaging or exam was sufficiently suspicious, after discussion with the head and neck team, to warrant treatment to definitive doses of RT (70 Gy). Results: Our cohort included 391 patients with SCC of the OCC who were treated with postoperative radiotherapy. 61% of patients were male, 35% had pT3-4 disease, 36% had pN2a-3 disease, 53% had PNI, 20% had LVI, 30% had ENE, and 14% had positive SM. The most common sites were oral tongue (46%), alveolar ridge (18%), and buccal mucosa (13%). 237 (61%) patients underwent postoperative PET/CT planning, and 165 patients (41%) were planned with CT only. Patients screened with post-operative PET/CT were more likely to be diagnosed with ER (46/237, 19.4%) than those simulated with CT only (6/154, 3.9%, p < 0.0001). Among patients simulated with PET/CT, 7%, 9%, 14%, and 35% of patients were diagnosed with ER for patients with 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF, respectively. Median follow-up was 4.1 years (95% CI 3.6 – 4.5). Among 52 patients with ER, 24 (49.0%) had local, 41 (83.7%) had regional, and 5 (10.2%) had distant recurrence. 17 (33%) of ER were biopsy proven. For patients with ER, 3-year freedom from locoregional recurrence, distant-metastasis free survival, and overall survival were 45.2% (95% CI 32% - 64%), 55% (95% CI 42% – 72%), and 43% (95% CI 30% - 61%), respectively. For patients without ER, use of postoperative PET/CT was associated with improved disease-free survival (HR 0.68, 95% CI 0.46 – 0.98, p = 0.041) and overall survival (HR 0.59, 95% CI 0.38 – 0.91, p = 0.019). Conclusions: Postoperative PET/CT may increase detection ER compared to CT simulation alone and improve risk stratification. Patients with ER are at high risk of locoregional failure, distant metastases, and mortality, despite salvage therapy. A prospective trial is underway at our institution to systemically study the role of PET/CT for detection of ER.

Efficacy and toxicity of postoperative external beam radiotherapy or chemoradiation for early-stage cervical cancer

2020 ◽  
Vol 30 (12) ◽  
pp. 1878-1886
Author(s):  
Mick J E van den Akker ◽  
Nanda Horeweg ◽  
Jogchum Jan Beltman ◽  
Carien L Creutzberg ◽  
Remi A Nout
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Risk Factor ◽  
High Risk ◽  
Early Stage ◽  
Free Survival ◽  
High Risk Factors ◽  
Early Stage Cervical Cancer ◽  
Risk Factors For Recurrence

ObjectiveThe aim of this study was to assess the impact of the evolving role of the addition of chemotherapy to postoperative radiotherapy on oncological outcomes and toxicity in patients with early-stage cervical cancer after radical hysterectomy.MethodsRetrospective cohort study of patients with stage IB1–IIB FIGO 2009 cervical cancer treated from November 1999 to May 2015 by primary surgery and radiotherapy (46–50.4 Gy in 1.8–2.0 Gy fractions) with or without concurrent cisplatin (40 mg/m2, 5–6 weekly cycles) with or without a brachytherapy boost. Chemotherapy was allocated depending on the risk factors for recurrence. Incidences of all outcomes were calculated using Kaplan–Meier’s methodology and compared by log-rank tests. Risk factors for recurrence and survival were identified using Cox’s proportional hazards models.ResultsA total of 154 patients were included, median follow-up was 9.6 years (IQR: 6.1–12.8). Five-year pelvic recurrence-free survival was 75.3%; 74.7% in patients with high-risk factors treated with radiotherapy; and 77.3% in those treated with chemoradiation (P=0.43). Distant metastasis-free survival at 5 years was 63.4%; 63.6% in high-risk patients after radiotherapy; and 57.1% after chemoradiation (P=0.36). Five-year overall survival was 63.9%: 66.8% and 51.6% after radiotherapy and after chemoradiation in patients with high-risk factors (P=0.37), respectively. Large tumor size was a risk factor for vaginal and pelvic recurrence, ≥2 involved lymph nodes was a significant risk factor for para-aortic recurrence and death. Mild treatment-related late toxicity was observed in 53.9% of the patients. Five-year severe (grade 3–5) late rectal, bladder, bowel, and vaginal toxicities were, respectively, 1.3%, 0%, 3.4%, and 0.9%. Any late severe toxicity was observed in 5.5% of patients treated with radiotherapy and in 15.3% of those treated with chemoradiation (P=0.07).ConclusionPostoperative (chemo)radiation for early-stage cervical cancer patients with risk factors for recurrence yields adequate pelvic tumor control, but overall survival is limited due to distant metastasis.

Efficacy and tolerability of adjuvant therapy in ≥70-year-old patients with T3N0M0 colorectal cancer: An observational study

2019 ◽  
Vol 26 (3) ◽  
pp. 619-631
Author(s):  
Abdullah Sakin ◽  
Nurgul Yasar ◽  
Suleyman Sahin ◽  
Serdar Arici ◽  
Saban Secmeler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Risk Group ◽  
Disease Free Survival ◽  
Old Patients ◽  
Free Survival ◽  
Disease Free

Background This study aimed to retrospectively investigate the efficacy and tolerability of adjuvant chemotherapy in ≥70-year-old patients with stage IIA (T3N0M0) colorectal cancer. Methods Lymphovascular invasion, perineural invasion, margin positivity, dissected lymph node count of <12, and presence of perforation/obstruction were accepted as risk factors. Those patients with at least one risk factor were regarded as having high risk. Results The study included 168 patients, among which 95 (56.5%) were male and 73 (43.5%) were female. The median age of patients was 73 years (range: 70–94). One hundred one (60.1%) patients were identified to have high risk. Eighty-one (87%) patients received 5-flourouracil+leucovorin and 12 (13%) patients received capecitabine regimens as adjuvant chemotherapy. The patients receiving capecitabine regimen had significantly higher rates of dose reduction at initiation and during the treatment. Among low-risk group, there was no statistically significant difference between patients with and without adjuvant chemotherapy in terms of disease-free survival or overall survival (p = 0.528 and p = 0.217, respectively). In high-risk group, patients receiving adjuvant chemotherapy significantly differed from those not receiving adjuvant chemotherapy in terms of median disease-free survival and overall survival (p = 0.009 and p < 0.001, respectively). While the grade, lymph node status, and adjuvant chemotherapy were identified as the most significant independent factors for disease-free survival, the most significant factors for overall survival were the age, Eastern Cooperative Oncology Group performance status, adjuvant chemotherapy, and recurrence. Conclusion The findings of our study showed improved disease-free survival and overall survival in high-risk ≥70-year-old patients who received adjuvant chemotherapy due to T3N0M0 colorectal cancer. We believe that 5-flourouracil+leucovorin or capecitabine regimens should be recommended for these older high-risk patients who could receive adjuvant chemotherapy regardless of age.

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