Azacitidine Prolongs Survival and Time to AML Transformation in High-Risk Myelodysplastic Syndrome (MDS) Patients ≥ 65 Years of Age.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2524-2524
Author(s):  
Lewis R. Silverman ◽  
David R. McKenzie ◽  
Bercedis L. Peterson ◽  
Erin P. Demakos ◽  
Neil T. Malone ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Supportive Care ◽  
Treatment Effect ◽  
Subgroup Analysis ◽  
Care Group ◽  
Patient Benefit ◽  
High Risk Patients ◽  
Subgroup Analyses ◽  
Risk Patients

Abstract The prognosis for patients with refractory anemia with excess blasts (RAEB) or RAEB in transformation (RAEB-T) ≥ 65 years of age has been poor. These high-risk patients are often not eligible for intensive induction/transplantation regimens or combination chemotherapies, leaving few treatment options besides supportive or palliative care. In the publication of the CALGB trial by Silverman et al (JCO2002;20:2429), no age- and/or risk- related subgroup analyses for azacitidine (Vidaza®) were presented. To assess the treatment effect of azacitidine versus supportive care on survival and time to AML transformation in a homogeneous sample of high-risk patients with MDS, we performed a subgroup analysis on the 191 patients included in the CALGB trial. All patients with a baseline diagnosis of RAEB or RAEB-T who were ≥ 65 years of age were included in the comparative analysis, using intent-to-treat (ITT) principles based on randomization to azacitidine or supportive care. Efficacy was analyzed using three survival endpoints: overall survival, time to death or AML transformation, and time to AML transformation. In all, 31 azacitidine patients and 37 supportive care patients met the criteria for this high-risk subgroup analysis. No significant differences in demographics or disease characteristics between the two groups were observed. For all three survival analyses, a statistically significant difference was observed for patients in the azacitidine group compared with those in the supportive care group. (Table) Median time to transformation to AML, in particular, was prolonged for 24 months in azacitidine patients compared with patients in the supportive care group. A sensitivity analysis of the overall survival results was conducted by performing 10 additional subgroup analyses based on ages ≥ 60 through ≥ 70 years in increments of one year with all overall survival results remaining significant (p < 0.05, except for 2 subgroup analyses based on ages ≥ 60 and ≥ 66 where both p-values were 0.051). The sensitivity results demonstrated robust patient benefit in the subgroup ≥ 65 years of age. The most common adverse event observed with azacitidine was myelosuppression, which decreased in frequency as therapy continued. Azacitidine provided clear treatment effect and patient benefit to this difficult-to-treat, high-risk group of RAEB and RAEB-T patients ≥ 65 years of age by significantly prolonging overall survival and time to AML transformation. Time of Even Analysis

scholarly journals A questionnaire survey on evaluation for penetration and compliance of the Japanese Guideline on Febrile Neutropenia among hematology-oncology physicians and surgeons

2021 ◽  
Author(s):  
Nobu Akiyama ◽  
Takuho Okamura ◽  
Minoru Yoshida ◽  
Shun-ichi Kimura ◽  
Shingo Yano ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Supportive Care ◽  
Questionnaire Survey ◽  
Primary Treatment ◽  
Beta Lactam ◽  
Clinical Practices ◽  
High Risk Patients ◽  
Mascc Score ◽  
Risk Patients

Abstract Purpose The Japanese Society of Medical Oncology published a guideline (GL) on febrile neutropenia (FN) in 2017. The study’s purpose is to reveal how widely GL penetrated among physicians and surgeons providing chemotherapy. Methods A questionnaire survey was conducted with SurveyMonkey™ for members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed with statistical text-analytics. Result A total of 800 responses were retrieved. Major respondents were experts with more than 10-year experience, physicians 54%, and surgeons 46%. Eighty-seven percent of respondents knew and used GL. Forty-eight percent assessed FN with Multinational Association of Supportive Care in Cancer (MASCC) score “always” or “more than half.” Eighty-one percent chose beta-lactam monotherapy as primary treatment in high-risk patients. Seventy-seven percent did oral antibacterial therapy in low-risk patients ambulatorily. Seventy-eight percent administered primary prophylactic G-CSF (ppG-CSF) in FN frequency ≥ 20% regimen. Fifty-nine percent did ppG-CSF for high-risk patients in FN frequency 10–20% regimen. Ninety-seven percent did not use ppG-CSF in FN frequency < 10% regimen. The medians of complete and complete plus partial compliance rates were 46.4% (range 7.0–92.8) and 77.8% (range 35.4–98.7). The complete compliance rates were less than 30% in seven recommendations, including the MASCC score assessment. Conclusion GL is estimated to be widely utilized, but some recommendations were not followed, presumably due to a mismatch with actual clinical practices in Japan.

Quality of Life and Overall Survival in High Risk Patients After Radical Cystectomy With a Simple Urinary Derivation

2015 ◽  
Vol 93 (6) ◽  
pp. 368-374
Author(s):  
Giuseppe Mucciardi ◽  
Luciano Macchione ◽  
Alessandro Galì ◽  
Antonina di Benedetto ◽  
Enrica Subba ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Overall Survival ◽  
High Risk ◽  
Radical Cystectomy ◽  
High Risk Patients ◽  
Risk Patients

Immunochemotherapy with Rituximab Improves Molecular CR Rate and Outcome In CD20+ B-Lineage Standard and High Risk Patients; Results of 263 CD20+ Patients Studied Prospectively In GMALL Study 07/2003

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 170-170 ◽  
Author(s):  
Dieter Hoelzer ◽  
Andreas Huettmann ◽  
Felix Kaul ◽  
Sebastian Irmer ◽  
Nadja Jaekel ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Relapse Rate ◽  
Remission Rate ◽  
Supportive Therapy ◽  
High Risk Patients ◽  
Tumour Load ◽  
Risk Patients ◽  
Standard Risk

Abstract Abstract 170 The effect of Rituximab in conjunction with a chemo induction and consolidation therapy was studied in CD20+, Ph/BCR-ABL negative B-precursor ALL (Pre-B/Common) in the GMALL Study 07/2003. The rationale were encouraging results with combined intensive chemotherapy and Rituximab in CD20+ adult Burkitt lymphoma / leukemia. Furthermore that in previous GMALL studies, improvement of B-precursor ALL by intensification of chemotherapy was limited and the observation that patients with CD20+ cells (antigen expression >20%) had an inferior outcome in adult ALL (Thomas et al. Blood 2009. 113;6330). Aim: In standard risk (SR) patients the aim was to increase the rate of molecular remission (Mol. CR) thereby decreasing the relapse rate and in high risk (HR) patients to reduce the pre-transplant tumour-load and thereby reducing the relapse rate after SCT which was 30–40% in previous GMALL studies. Materials and Methods: Adult ALL patients (15 – 55 years) with standard risk B-precursor ALL being CD20 pos. received Rituximab 375 mg/m2 at day -1 before each induction course (phase I and II), the re-induction course and before each of the six consolidations for a total of 8 doses. High Risk patients, defined as WBC > 30.000 and/or late CR > 4 weeks, which are candidates for a stem cell transplantation in CR 1 after wk 16, received Rituximab three times (d -1 ind. I/II and Cons. I) before SCT. Patients receiving Rituximab were compared with earlier CD20+ patients in the GMALL study 07/2003 with identical chemo- and supportive therapy but no Rituximab. MRD method and chemo backbone was described earlier [Brüggemann, Blood 2006: 107;1116]. Results: A total of 263 CD20 pos. patients were analyzed in the GMALL study 07/2003; 196 were SR and 67 HR patients. 181 received Rituximab (R+ arm) and were compared to a cohort of 82 patients earlier recruited without Rituximab (R- arm). In the SR there was no difference in the results of induction therapy with a CR rate of 94 % and 91 % in the R+ vs. R- patients. There was also no difference in ED rate 5% vs. 3% or failure/PR 1% vs. 5%. However, MRD course differed substantially. Decrease in MRD load in the R+ vs. R- arm was faster with a Mol CR (MRD <10-4) rate of 57% vs. 27% at day 24 and of 90% vs. 59% at wk 16. Probability for continuous complete remission (CCR) at 5 years was 80% vs. 47% for R+ vs. R- pts. and for overall survival 71% vs. 57%. In the cohort of 67 HR patients the CR rate for R+ vs. R- was 81% vs. 88% due to a higher rate of failure/PR 12% vs. 8%. The ED rates in the R+ vs. R- arm were 7% vs. 4%. There was a higher Mol CR rate at wk 16 in the R+ arm vs. R- with 64% vs. 40%. Overall survival for HR patients at 5 yrs was 55% vs. 36% in the R+ vs. R- group. When only the HR cohort with SCT in CR1 is considered (in 69 % +R and 90% -R SCT in CR1 were performed) the CCR probability was superior for the R+ vs. R- with 67% vs. 37%, due to a lower relapse rate. Conclusion: Intensive chemo- plus immunotherapy with Rituximab is feasible in adult patients with B-precursor ALL in the context of the GMALL protocol 07/2003. In standard risk patients, the complete remission rate was comparable. There was however a faster and higher Mol. CR rate in the Rituximab cohort, with an improvement in remission duration and overall survival. In high risk patients the Mol. CR rate was also higher in the R+ arm and the relapse rate after SCT lower, but probably more Rituximab doses are needed in this patient cohort to reduce the tumour load before SCT further. Supported by Deutsche Krebshilfe 70–2657-Ho2 and in part by Hoffmann La Roche. Disclosures: Off Label Use: Rituximab: activity against CD20 pos. ALL cells.

scholarly journals Prognostic value of preoperative circulating tumor cells counts in patients with UICC stage I-IV colorectal cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252897
Author(s):  
Thaer S. A. Abdalla ◽  
Jan Meiners ◽  
Sabine Riethdorf ◽  
Alexandra König ◽  
Nathaniel Melling ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Stage I ◽  
Clinicopathological Parameters ◽  
Curative Intent ◽  
High Risk Patients ◽  
Risk Patients

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. There is an urgent need to identify prognostic markers for patients undergoing curative resection of CRC. The detection of circulating tumor cells in peripheral blood is a promising approach to identify high-risk patients with disseminated disease in colorectal cancer. This study aims to evaluate the prognostic relevance of preoperative CTCs using the Cellsearch® system (CS) in patients, who underwent resection with curative intent of different stages (UICC I-IV) of colorectal cancer. Out of 91 Patients who underwent colorectal resection, 68 patients were included in this study. CTC analysis was performed in patients with CRC UICC stages I-IV immediately before surgery. Data were correlated with clinicopathological parameters and patient outcomes. One or more CTCs/7.5 mL were detected in 45.6% (31/68) of patients. CTCs were detected in all stages of the Union of International Cancer Control (UICC), in stage I (1/4, 25%), in stage II (4/12, 33.3%), in stage III (5/19, 26.3%) and in stage IV (21/33, 63.6%). The detection of ≥ 1 CTCs/ 7.5ml correlated to the presence of distant overt metastases (p = 0.014) as well as with shorter progression-free (p = 0.008) and overall survival (p = 0.008). Multivariate analyses showed that the detection of ≥ 1 CTCs/ 7.5ml is an independent prognostic indicator for overall survival (HR, 3.14; 95% CI, 1.18–8.32; p = 0.021). The detection of CTCs is an independent and strong prognostic factor in CRC, which might improve the identification of high-risk patients in future clinical trials.

scholarly journals Evaluation of conditional treatment effects of adjuvant treatments on patients with synovial sarcoma using Bayesian subgroup analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sung Wook Seo ◽  
Jisoo Kim ◽  
Jihye Son ◽  
Sungbin Lim
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
High Risk ◽  
Propensity Score ◽  
Synovial Sarcoma ◽  
Treatment Effects ◽  
Spindle Cell ◽  
Large Tumor ◽  
Subgroup Analyses ◽  
Risk Patients

Abstract Background The impact of adjuvant chemotherapy or radiation therapy on the survival of patients with synovial sarcoma (SS), which is a rare soft-tissue sarcoma, remains controversial. Bayesian statistical approaches and propensity score matching can be employed to infer treatment effects using observational data. Thus, this study aimed to identify the individual treatment effects of adjuvant therapies on the overall survival of SS patients and recognize subgroups of patients who can benefit from specific treatments using Bayesian subgroup analyses. Methods We analyzed data from patients with SS obtained from the surveillance, epidemiology, and end results (SEER) public database. These data were collected between 1984 and 2014. The treatment effects of chemotherapy and radiation therapy on overall survival were evaluated using propensity score matching. Subgroups that could benefit from radiation therapy or chemotherapy were identified using Bayesian subgroup analyses. Results Based on a stratified Kaplan–Meier curve, chemotherapy exhibited a positive average causal effect on survival in patients with SS, whereas radiation therapy did not. The optimal subgroup for chemotherapy includes the following covariates: older than 20 years, male, large tumor (longest diameter > 5 cm), advanced stage (SEER 3), extremity location, and spindle cell type. The optimal subgroup for radiation therapy includes the following covariates: older than 20 years, male, large tumor (longest diameter > 5 cm), early stage (SEER 1), extremity location, and biphasic type. Conclusion In this study, we identified high-risk patients whose variables include age (age > 20 years), gender, tumor size, tumor location, and poor prognosis without adjuvant treatment. Radiation therapy should be considered in the early stages for high-risk patients with biphasic types. Conversely, chemotherapy should be considered for late-stage high-risk SS patients with spindle cell types.

CapRI: Final results of the open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon-α2b (CRI) versus 5-FU alone for patients with resected pancreatic adenocarcinoma (PAC).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA4012-LBA4012 ◽  
Author(s):  
A. Marten ◽  
J. Schmidt ◽  
J. Debus ◽  
S. Harig ◽  
K. Lindel ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Overall Survival ◽  
High Risk ◽  
Bolus Injection ◽  
Phase Iii ◽  
External Beam Radiation ◽  
High Risk Patients ◽  
Significant Difference ◽  
Risk Patients

LBA4012 Background:Adjuvant chemomonotherapy in PAC results in five-year survival of 21% with median overall survival (mOS) of 23 months. Phase II trials evaluating adjuvant CRI showed promising results (mOS 27-44 months). Methods: Patients with an R0/R1 resection for PAC were randomized <12 weeks of surgery to receive either 5-Fluorouracil (200mg/m2/day, CI); Cisplatin (weekly 30mg/m2) and 3 million units IFN-α (three times a week) for 5.5 weeks combined with external beam radiation (50.4Gy in 28 fractions) followed by two more cycles of continuous 5-FU or 5FU/FA (FA, 20 mg/m2, iv bolus injection followed by 5-FU, 425 mg/m2, iv bolus injection given 1-5d every 28 days) for 6 months. Patients treated with CRI were challenged prior to therapy with a single dose of IFN-α. The primary outcome measure was overall survival; the secondary measures were toxicity, progression free survival and quality of life. 110 patients were calculated to detect a difference in hazard on level α= 0.05 and with a power of 80%. Results: 110 patients from five centers in Germany and Italy were randomized from July 2004 and December 2007. Median (range) age was 63 (33-77) years; 60 (57%) were men. 104 (95%) were T3 tumors, 87 (79%) were node positive and 43 (39%) were R1 resections, and 33 (30%) were poorly differentiated tumors. Grade 3 or 4 toxicity (mainly neutropenia) was observed in 68% of CRI and 16% of 5FU/FA (mainly diarrhea). Side effects during the multimodular cycle 1 were manageable and patients recovered completely. There was no difference in quality of life between the treatment groups. Final analysis was carried out on an intention to treat basis with a minimum of 2 years follow-up. Median survival of patients treated with 5FU/FA was 28.5 [95% CI: 19.5, 38.6] months and for patients treated with CRI this was 32.1 [95% CI: 22.8, 42.2] months. Although survival curves are clearly separated the log-rank analysis revealed no statistically significant difference in survival estimates. There was a clear trend towards better response for high risk patients (R1, start of treatment > 8 weeks after surgery; p=0.11). CRI reduced the risk of local recurrence (29.3% vs. 55.6%; p=0.014). Pre-planned testing for predictive markers showed that patients treated with CRI who responded to single IFN-α challenge with a decrease in T helper cells and especially regulatory T cells or with a pronounced increase in NK cell mediated cytotoxicity had a significantly longer survival. Conclusions: This is the highest ever reported mOS for adjuvant PAC in a randomized trial. Unfortunately, this underpowered trial was not able to address the significance of CRI in PAC satisfactorily. There is evidence that especially high risk patients benefit from CRI; local control improved significantly. A strong immune response to a single IFN-α challenge is significantly associated with a good outcome. Confirmatory trials are needed. [Table: see text]

Trends in conditional survival and predictors of late death in neuroblastoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10533-10533
Author(s):  
Hannah Olsen ◽  
Kevin M. Campbell ◽  
Rochelle Bagatell ◽  
Steven G. DuBois
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Primary Site ◽  
Conditional Survival ◽  
Late Death ◽  
High Risk Patients ◽  
Risk Patients ◽  
Over Time

10533 Background: Significant advances in the treatment of neuroblastoma have been made in the past several decades. There are scant data examining how these improvements have changed over time and differentially affected conditional survival among high- and non-high-risk patient groups. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results Database. We analyzed clinical characteristics and survival outcomes for 4717 neuroblastoma patients. Kaplan-Meier methods were used to estimate overall survival (OS) and conditional overall survival (COS) conditioned on having survived 1, 2, or 5 years from diagnosis, with estimates compared between groups using log-rank tests. Results: Five-year OS was 41.46% (95% CI 38.77-44.13) for the high-risk group and 91.13% (95% CI 89.49-92.53) for the non-high-risk group. Both groups saw significant improvements in OS by decade (p<0.001). Five-year COS among 1-year survivors was 52.69% (95% CI 38.77-44.13) for the high-risk group and 96.75% (95% CI 95.57-97.62) for the non-high-risk group. One-year survivors in the high-risk group showed a statistically significant improvement in COS over time. No difference in COS was observed among 5-year high-risk survivors. There were no statistically significant changes in COS over time for 1- and 5-year survivors in the non-high-risk group. In the high-risk and non-high-risk groups, 82% and 32% of late deaths (>5 years from diagnosis) were attributable to cancer, respectively. Statistically significant adverse prognostic factors for late death were age >1 year at diagnosis, metastatic disease, and non-thoracic primary site (p=0.001). Conclusions: Improvements in COS over time have largely benefited high-risk patients, though they are still at higher risk for late death due to cancer when compared to non-high-risk patients. Age, stage, and primary site, but not treatment decade, influence outcomes among 5-year survivors. [Table: see text]

Sample size estimates for determining treatment effects in high-risk patients with early relapsing-remitting multiple sclerosis

2003 ◽  
Vol 9 (3) ◽  
pp. 289-292 ◽  
Author(s):  
Thomas F Scott ◽  
Carol J Schramke ◽  
Gary Cutter
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Sample Size ◽  
Treatment Effect ◽  
Significant Treatment Effect ◽  
Significant Treatment ◽  
High Risk Patients ◽  
Treatment Trials ◽  
Relapsing Remitting ◽  
Risk Patients

Background: Risk factors for short-term progression in early relapsing-remitting MS have been identified recently. Previously we determined potential risk factors for rapid progression of early relapsing-remitting MS and identified three groups of high-risk patients. These non-mutually exclusive groups of patients were drawn from a consecutively studied sample of 98 patients with newly diagnosed MS. High-risk patients had a history of either poor recovery from initial attacks, more than two attacks in the first two years of disease, or a combination of at least four other risk factors. Objective: To determine differences in sample sizes required to show a meaningful treatment effect when using a high-risk sample versus a random sample of patients. Methods: Power analyses were used to calculate the different sample sizes needed for hypothetical treatment trials. Results: We found that substantially smaller numbers of patients should be needed to show a significant treatment effect by employing these high-risk groups of patients as compared to a random population of MS patients (e.g., 58% reduction in sample size in one model). Conclusion: The use of patients at higher risk of progression to perform drug treatment trials can be considered as a means to reduce the number of patients needed to show a significant treatment effect for patients with very early MS.

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