scholarly journals Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3025-3031 ◽  
Author(s):  
Francesca Gay ◽  
Alessandra Larocca ◽  
Pierre Wijermans ◽  
Federica Cavallo ◽  
Davide Rossi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hazard Ratio ◽  
Novel Agents ◽  
Maximal Response ◽  
Term Outcome ◽  
Long Term Outcome ◽  
The Impact

AbstractComplete response (CR) was an uncommon event in elderly myeloma patients until novel agents were combined with standard oral melphalan-prednisone. This analysis assesses the impact of treatment response on progression-free survival (PFS) and overall survival (OS). We retrospectively analyzed 1175 newly diagnosed myeloma patients, enrolled in 3 multicenter trials, treated with melphalan-prednisone alone (n = 332), melphalan-prednisone-thalidomide (n = 332), melphalan-prednisone-bortezomib (n = 257), or melphalan-prednisone-bortezomib-thalidomide (n = 254). After a median follow-up of 29 months, the 3-year PFS and OS were 67% and 27% (hazard ratio = 0.16; P < .001), and 91% and 70% (hazard ratio = 0.15; P < .001) in patients who obtained CR and in those who achieved very good partial response, respectively. Similar results were observed in patients older than 75 years. Multivariate analysis confirmed that the achievement of CR was an independent predictor of longer PFS and OS, regardless of age, International Staging System stage, and treatment. These findings highlight a significant association between the achievement of CR and long-term outcome, and support the use of novel agents to achieve maximal response in elderly patients, including those more than 75 years. This trial was registered at www.clinicaltrials.gov as #NCT00232934, #ISRCTN 90692740, and #NCT01063179.

Does 30-Day Readmission Affect Long-term Outcome Among Glioblastoma Patients?

Neurosurgery ◽  
2013 ◽  
Vol 74 (2) ◽  
pp. 196-205 ◽  
Author(s):  
Miriam Nuño ◽  
Diana Ly ◽  
Alicia Ortega ◽  
J.Manuel Sarmiento ◽  
Debraj Mukherjee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hazard Ratio ◽  
Newly Diagnosed ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Newly Diagnosed Glioblastoma ◽  
Index Hospital ◽  
Medicare Database ◽  
The Impact

Abstract BACKGROUND: Research on readmissions has focused mainly on the economic and resource burden it places on hospitals. OBJECTIVE: To evaluate the effect of 30-day readmission on overall survival among newly diagnosed glioblastoma multiforme (GBM) patients. METHODS: A nationwide cohort of GBM patients diagnosed between 1991 and 2007 was studied using the Surveillance, Epidemiology and End Results Medicare database. Multivariate models were used to determine factors associated with readmission and overall survival. Odds ratio, hazard ratio, 95% confidence interval, and P values were reported. Complete case and multiple imputation analyses were performed. RESULTS: Among the 2774 newly diagnosed GBM patients undergoing surgery at 442 hospitals nationwide, 437 (15.8%) were readmitted within 30 days of the index hospitalization. Although 63% of readmitted patients returned to the index hospital where surgery was performed, a significant portion (37%) were readmitted to nonindex hospitals. The median overall survival for readmitted patients (6.0 months) was significantly shorter than for nonreadmitted (7.6 months; P &lt; .001). In a confounder-adjusted imputed model, 30-day readmission increased the hazard of mortality by 30% (hazard ratio, 1.3; P &lt; .001). Neurological symptoms (30.2%), thromboembolic complications (19.7%), and infections (17.6%) were the leading reasons for readmission. CONCLUSION: Prior studies that have reported only the readmissions back to index hospitals are likely underestimating the true 30-day readmission rate. GBM patients who were readmitted within 30 days had significantly shorter survival than nonreadmitted patients. Future studies that attempt to decrease readmissions and evaluate the impact of reducing readmissions on patient outcomes are needed.

Importance of Achieving a Complete Response in Multiple Myeloma, and the Impact of Novel Agents

2010 ◽  
Vol 28 (15) ◽  
pp. 2612-2624 ◽  
Author(s):  
Asher A. Chanan-Khan ◽  
Sergio Giralt
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Significance ◽  
Complete Response ◽  
Maximal Response ◽  
Prognostic Impact ◽  
Long Term Outcomes ◽  
First Line ◽  
The Impact

The goal of treatment for multiple myeloma (MM) is to improve patients' long-term outcomes. One important factor that has been associated with prolonged progression-free and overall survival is the quality of response to treatment, particularly achievement of a complete response (CR). There is extensive evidence from clinical studies in the transplant setting in first-line MM demonstrating that CR or maximal response post-transplant is significantly associated with prolonged progression-free and overall survival, with some studies demonstrating a similar association with postinduction response. Supportive evidence is also available from studies in the nontransplant and relapsed settings. With the introduction of bortezomib, thalidomide, and lenalidomide, higher rates of CR are being achieved in both first-line and relapsed MM compared with previous chemotherapeutic approaches, thereby potentially improving long-term outcomes. While standard CR by established response criteria has been shown to have differential prognostic impact compared with lesser responses, increasingly sensitive analytic techniques are now being explored to define more stringent degrees of CR or elimination of minimal residual disease (MRD), including multiparameter flow cytometry and polymerase chain reaction. Demonstrating eradication of MRD by these techniques has already been shown to predict for improved outcomes. Here, we review the prognostic significance of achieving CR in MM and highlight the importance of CR as an increasingly realizable goal at all stages of treatment. We discuss clinical management issues and provide recommendations relevant to practicing oncologists, such as the routine use of sensitive techniques for assessment of disease status to inform evidence-based decisions on optimal patient management.

scholarly journals Hepatocellular Carcinoma in Liver Cirrhosis: Surgical Resection versus Transarterial Chemoembolization—A Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Teodor Kapitanov ◽  
Ulf P. Neumann ◽  
Maximilian Schmeding
Keyword(s):  
Overall Survival ◽  
Liver Resection ◽  
Surgical Resection ◽  
Meta Analysis ◽  
Hazard Ratio ◽  
Long Term Results ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Short And Long Term

We compare the value of TACE to liver resection for patients with BCLC stage A and B HCC. For patients with HCC in cirrhosis LT is the treatment of choice. TACE represents the current standard for unresectable BCLC stage B patients not eligible for LT. Recently liver resection for HCC and significant cirrhosis has become increasingly popular. A systematic search of the literature and meta-analysis was conducted to identify studies, reporting short- and long-term results of hepatic resection versus TACE for HCC treatment. The data were analyzed regarding the odds for 30-day mortality and hazard ratio for overall-survival. 12 studies comparing short- and long-term outcome of HR versus TACE for HCC were identified. Peri-interventional mortality and overall survival were investigated. Peri-interventional mortality was higher for surgical resection (n.s.), and overall-survival was significantly better for surgically treated patients at one year (P=0.002) and 3 years (P≤0.00001). The hazard ratio of overall-survival for all twelve studies was 0.70 (P=0.0001) and significantly in favor of surgical treatment. Although large RCTs are missing and the available data are limited and not homogeneous a reappraisal of the current treatment guidelines should be considered based on the superior long-term outcome for surgically treated patients.

scholarly journals Influence of Body Mass Index on Long-Term Outcome in Patients with Rectal Cancer—A Single Centre Experience

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 609 ◽  
Author(s):  
Kalb ◽  
Langheinrich ◽  
Merkel ◽  
Krautz ◽  
Brunner ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Rectal Cancer ◽  
Overall Survival ◽  
Local Recurrence ◽  
Distant Metastasis ◽  
Hazard Ratio ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Obesity Class

Background: Excess bodyweight is known to influence the risk of colorectal cancer; however, little evidence exists for the influence of the body mass index (BMI) on the long-term outcome of patients with rectal cancer. Methods: We assessed the impact of the BMI on the risk of local recurrence, distant metastasis and overall—survival in 612 patients between 2003 and 2010 after rectal cancer diagnosis and treatment at the University Hospital Erlangen. A Cox-regression model was used to estimate the hazard ratio and multivariate risk of mortality and distant-metastasis. Median follow up-time was 58 months. Results: Patients with obesity class II or higher (BMI ≥ 35 kg/m2, n = 25) and patients with underweight (BMI < 18.5 kg/m2, n = 5) had reduced overall survival (hazard ratio (HR) = 1.6; 95% confidence interval (CI) 0.9–2.7) as well as higher rates of distant metastases (hazard ratio HR = 1.7; 95% CI 0.9–3.3) as compared to patients with normal bodyweight (18.5 ≤ BMI < 25 kg/m2, n = 209), overweight (25 ≤ BMI <30 kg/m2, n = 257) or obesity class I (30 ≤ BMI <35 kg/m2, n = 102). There were no significant differences for local recurrence. Conclusions: Underweight and excess bodyweight are associated with lower overall survival and higher rates of distant metastasis in patients with rectal cancer.

scholarly journals Phase II Randomized Comparison of Topotecan Plus Cyclophosphamide Versus Topotecan Alone in Children With Recurrent or Refractory Neuroblastoma: A Children's Oncology Group Study

2010 ◽  
Vol 28 (24) ◽  
pp. 3808-3815 ◽  
Author(s):  
Wendy B. London ◽  
Christopher N. Frantz ◽  
Laura A. Campbell ◽  
Robert C. Seeger ◽  
Babette A. Brumback ◽  
...  
Keyword(s):  
Causal Inference ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Mycn Amplification ◽  
Term Outcome ◽  
Long Term Outcome

PurposeSingle-agent topotecan (TOPO) and combination topotecan and cyclophosphamide (TOPO/CTX) were compared in a phase II randomized trial in relapsed/refractory neuroblastoma. Because responders often underwent further therapies, novel statistical methods were required to compare the long-term outcome of the two treatments.Patients and MethodsChildren with refractory/recurrent neuroblastoma (only one prior aggressive chemotherapy regimen) were randomly assigned to daily 5-day topotecan (2 mg/m2) or combination topotecan (0.75 mg/m2) and cyclophosphamide (250 mg/m2). A randomized two-stage group sequential design enrolled 119 eligible patients. Toxicity and response were estimated. Long-term outcome of protocol therapy was assessed using novel methods—causal inference—which allowed adjustment for the confounding effect of off-study therapies.ResultsSeven more responses were observed for TOPO/CTX (complete response [CR] plus partial response [PR], 18 [32%] of 57) than TOPO (CR+PR, 11 [19%] of 59;P = .081); toxicity was similar. At 3 years, progression-free survival (PFS) and overall survival (OS) were 4% ± 2% and 15% ± 4%, respectively. PFS was significantly better for TOPO/CTX (P = .029); there was no difference in OS. Older age at diagnosis and lack of MYCN amplification predicted increased OS (P < .05). Adjusting for randomized treatment effect and subsequent autologous stem-cell transplantation, there was no difference between TOPO and TOPO/CTX in terms of the proportion alive at 2 years.ConclusionTOPO/CTX was superior to TOPO in terms of PFS, but there was no OS difference. After adjustment for subsequent therapies, no difference was detected in the proportion alive at 2 years. Causal inference methods for assessing long-term outcomes of phase II therapies after subsequent treatment can elucidate effects of initial therapies.

Long-Term Outcome of B-CLL Patients Treated in a Prospective Trial Evaluating Combination of Oral Fludarabine and Cyclophosphamide As Frontline Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1795-1795
Author(s):  
Romain Guièze ◽  
Olivier Tournilhac ◽  
Karim Maloum ◽  
Stéphane Leprêtre ◽  
Corinne Haioun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
Mutational Status

Abstract Abstract 1795 Introduction. The combination of fludarabine and cyclophosphamide (FC) has become the core combination of modern frontline chemotherapy for fit and young B-CLL patients (pts). Recently the association with rituximab to FC (IV administration) has been shown to increase the response and extend both progression free survival (PFS) and overall survival (OS) in untreated pts (Hallek et al., Lancet 2010). So far few data are available concerning the very long term outcome of pts treated by FC containing regimen. Methods. We previously reported a prospective phase II trial (Cazin et al., BJH 2008) of the oral combination of FC over 5 days in 75 patients with untreated B-CLL and less than 66 years old. The study was conducted between October 1999 and February 2001. Briefly, oral FC then demonstrated high efficacy with overall response rate (ORR) and complete response (CR) rate of 80% and 53% respectively despite the absence of rituximab in this regimen. We here propose to examine 10-year end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN) by updating survival data of all the pts incuded in this trial. Results. With a median follow-up of 10.7 years, the median 10-year OS was 51.7%. Responders presented better 10-year OS than non-responders (57% vs. 38%, p=0.031) but quality of response (CR vs. PR) did not significantly impact 10-year OS. A major prognostic impact of IGVH mutational status could be observed since 10-year OS was 81% for mutated patients vs. 44% for unmutated pts (p=0.012). The median 10-year PFS was 30% and clearly influenced by the mutational status (50% if mutated profile vs. 12% if unmutated profile, p=0.02). However there is no trend of a plateau and even long term responding patients still relapse with time. Finally, only one patient developed t-MN but 9 others presented solid neoplasms. Conclusion. Long-term follow-up of B-CLL patients prospectively treated in a phase II clinical trial demonstrates extended OS and PFS with oral FC without high risk of t-MN. Disclosures: No relevant conflicts of interest to declare.

Achievement of Complete Response Is Important for Longer Overall Survival in Patients with Newly Diagnosed Myeloma: A Single-Institutional Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5115-5115
Author(s):  
Kanichi Iwama ◽  
Tomotaka Ugai ◽  
Hiroki Sugihara ◽  
Masayuki Yamakura ◽  
Masami Takeuchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Partial Response ◽  
Complete Response ◽  
Novel Agents ◽  
Response To Treatment ◽  
Prognostic Impact ◽  
Female Ratio ◽  
Best Response ◽  
The Impact

Abstract Abstract 5115 INTRODUCTION. Even with the introduction of novel therapeutic agents, including thalidomide, bortezomib, and lenalidomide, multiple myeloma (MM) is an incurable disease. Deeper responses, such as complete response (CR) and very good partial response (VGPR), are major goals of treatment to obtain long-term overall response (OS) and progression-free response (PSF) in patients with MM. Recent large randomized retrospective studies also suggested improved OS and PFS in patients who achieved deeper responses. However, the prognostic impact of achieving CR or VGPR remains controversial. In addition, these studies included selected patients that may not be representative of the general population. Therefore, we analyzed cases in our database to evaluate the impact of treatment response on the outcome of consecutive patients with symptomatic MM who were treated with chemotherapeutic regimens containing novel agents over the past 6 years at our institution in Kamogawa City, Japan. PATIENTS AND METHODS. We included 97 consecutive patients treated at our institution between April 2005 and May 2011. The study population consisted of 56 male and 41 female patients with a median age of 70 years old (range: 45 −90). Due to the rapid changes in treatment modality and government approval of novel agents in myeloma during this period, initial treatment could not be uniformly categorized, but all patients received chemotherapy regimens containing at least one novel agent, including thalidomide, bortezomib, and lenalidomide. These patients were thought to be more representative of the general myeloma population. Seventy-seven (79.4%), 27 (38.6%), and 55 (56.7%) patients received bortezomib-, lenalidomide-, and thalidomide-containing regimens, respectively. Treatment responses were assessed using the International Myeloma Working Group (IMWG) criteria with minor modifications, and the best response to treatment during the course of disease was evaluated. Immunofixation test and serum free light chain measurements were performed for confirmation of CR and stringent CR. OS was calculated from the time of diagnosis until the date of death from any cause or the date on which the patient was last known to be alive. Univariate and multivariate analyses were performed for the following variables: age at diagnosis, International Staging System (ISS), and best response achieved. RESULT. The median age of patients was 71 y.o. (range: 49 −90 y.o.), and the male to female ratio was 56:41. The best responses to treatment were as follows: CR was obtained in 19 cases (19.6%), VGPR in 29 (29.9%), partial response (PR) in 34 (35.0%), and stable disease (SD) or less in 15 (15.4%). Baseline characteristics according to best response achieved in patients who achieved CR, VGPR, PR, and SD or less were similar among the patients ≥70 y.o. vs. ≤70 y.o. Patients' age has no impact on the response to treatment. With a median follow-up of 25 months, Kaplan–Meier estimated 3-year and 5-year overall survival (OS) rates were 67.2% and 35.0%, respectively. The 3- and 5-year OS were 100% in patients with CR, which were significantly superior in patients with VGPR (3-y 70%, 5-y 55.0%) and PR (3-y 60%, 5-y 23.0%). The 3- and 5-year OS were not significantly different between patients with VGPR and PR. Normalization of FLC kappa/Lambda ratio was observed in 15 of 19 (80%) patients with CR, 15 of 29 (51%) with VGPR, 4 of 34 (6.6%) in PR, and in none of 15 (0%) in SD or less. Patients who showed normalization of FLC kappa/Lambda ratio had significant OS benefit compared to those who did not. Proportional hazard Cox models showed that patients with ISS stage I/II had better 5-year OS rate compared to patients with stage III (51%; 20%, P = 0.005). However, there was no association between ISS stage and achievement of CR. CONCLUSION. The results of the present study highlighted the importance of achieving CR, not PR or VGPR, and normalization of FLC kappa/Lambda ratio for obtaining long-term OS in patients with MM regardless of age or ISS stage. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Minimal Residual Disease Dynamics after Venetoclax-Obinutuzumab Treatment: Extended Off-Treatment Follow-up From the Randomized CLL14 Study

2021 ◽  
Author(s):  
Othman Al-Sawaf ◽  
Can Zhang ◽  
Tong Lu ◽  
Michael Z. Liao ◽  
Anesh Panchal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Hazard Ratio ◽  
Lymphocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Minimal Residual

PURPOSE The CLL14 study has established one-year fixed-duration treatment of venetoclax and obinutuzumab (Ven-Obi) for patients with previously untreated chronic lymphocytic leukemia. With all patients off treatment for at least three years, we report a detailed analysis of minimal residual disease (MRD) kinetics and long-term outcome of patients treated in the CLL14 study. PATIENTS AND METHODS Patients were randomly assigned to receive six cycles of obinutuzumab with 12 cycles of venetoclax or 12 cycles of chlorambucil (Clb-Obi). Progression-free survival (PFS) was the primary end point. Key secondary end points included rates of undetectable MRD and overall survival. To analyze MRD kinetics, a population-based growth model with nonlinear mixed effects approach was developed. RESULTS Of 432 patients, 216 were assigned to Ven-Obi and 216 to Clb-Obi. Three months after treatment completion, 40% of patients in the Ven-Obi arm (7% in the Clb-Obi arm) had undetectable MRD levels < 10−6 by next-generation sequencing in peripheral blood. Median MRD doubling time was longer after Ven-Obi than Clb-Obi therapy (median 80 v 69 days). At a median follow-up of 52.4 months, a sustained significant PFS improvement was observed in the Ven-Obi arm compared with Clb-Obi (median not reached v 36.4 months; hazard ratio 0.33; 95% CI, 0.25 to 0.45; P < .0001). The estimated 4-year PFS rate was 74.0% in the Ven-Obi and 35.4% in the Clb-Obi arm. No difference in overall survival was observed (hazard ratio 0.85; 95% CI, 0.54 to 1.35; P = .49). No new safety signals occurred. CONCLUSION Appearance of MRD after Ven-Obi is significantly slower than that after Clb-Obi with more effective MRD reduction. These findings translate into a superior long-term efficacy with the majority of Ven-Obi–treated patients remaining in remission.

Sustained Tumor Control With MAPK Inhibition in BRAF V600–Mutant Adult Glial and Glioneuronal Tumors

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012330
Author(s):  
Giulia Berzero ◽  
Luisa Bellu ◽  
Capucine Baldini ◽  
François Ducray ◽  
David Guyon ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Adult Patients ◽  
Tumor Control ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Glioneuronal Tumors

Objective:To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients with BRAF V600-mutant glial and glioneuronal tumors (GGNT), we analyzed tumor response and long-term outcome in a retrospective cohort.Methods:We performed a retrospective search in the institutional databases of six neuroncology departments for adult patients with recurrent or disseminated BRAF V600-mutant GGNT treated with RAFi/MEKi.Results:Twenty-eight adults with recurrent or disseminated BRAF V600-mutant gangliogliomas (n=9), pleomorphic xanthoastrocytomas (n=9), and diffuse gliomas (n=10) were included in the study. At the time treatment with RAFi/MEKi was started, all tumors displayed radiological features of high-grade neoplasms. Thirteen patients received RAFi as single agents [vemurafenib (n=11), dabrafenib (n=2)], and 15 combinations of RAFi/MEKi [vemurafenib+cobimetinib (n=5), dabrafenib+trametinib (n=10)]. Eleven patients achieved a partial or complete response (11/28, 39%), with a median reduction of -78% in their tumor burden. Responders experienced a median increase of 10 points in their Karnofsky Performance Status (KPS) and a median progression-free survival of 18 months, which was longer than achieved with first-line treatment (i.e., 7 months, p=0.047). Responders had better KPS (p=0.018), tended to be younger (p=0.061) and to be treated earlier (p=0.099) compared to non-responders. Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in two. On univariate and multivariate analyses, response to RAFi/MEKi was an independent predictor of overall survival.Conclusions:Our study highlights the clinical benefits of RAFi/MEKi in adult patients with BRAF-mutant GGNT, encourages the systematic screening and rechallenge in responders.

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