Long-term outcomes of stereotactic body radiotherapy for low- and intermediate-risk prostate adenocarcinoma: A multi-institutional consortium study.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 84-84 ◽  
Author(s):  
Amar Upadhyaya Kishan ◽  
Alan J. Katz ◽  
Constantine Mantz ◽  
Fang-I Chu ◽  
Limor Appelbaum ◽  
...  
Keyword(s):  
Risk Group ◽  
Survival Rates ◽  
Low Risk ◽  
Rank Test ◽  
Intermediate Risk ◽  
Long Term Outcomes ◽  
Log Rank Test ◽  
Gu Toxicity ◽  
Grade 3

84 Background: While a growing body of evidence supports the use of stereotactic body radiotherapy (SBRT) for the treatment of low- and intermediate-risk prostate adenocarcinoma (PCa), some trepidation exists regarding its long-term efficacy and safety. Methods: Men with low- and intermediate-risk PCa, as defined per the National Comprehensive Cancer Network guidelines, who were enrolled on various institutional phase II trials of SBRT between 2000-2012 were included in a multi-institutional consortium. Biochemical relapse (BCR) was defined as PSA > “nadir +2” or initiation of androgen deprivation therapy (ADT). Toxicity data were scored according to the CTCAE v 3.0 or Radiation Therapy Oncology Group scoring systems. Results: A total of 1644 men were eligible for analysis, with a median followup of 7.2 years. 297 patients (18.1%) had at least 9 years of followup. Fractionation schemes ranged from 33.50-40 Gy in 4-5 fractions. 892 patients had low-risk disease and 752 had intermediate-risk disease. 59 patients (3.6%) received short-term ADT. 100 patients (6.0%) experienced BCR, and 7 (0.4%) experienced distant metastases. No patients died of PCa. By Kaplan-Meier analysis, 5- and 10-year BCR-free survival rates were 98% and 94% in the low-risk group and 96% and 90% in the intermediate-risk group (p < 0.05 by log-rank test). 5- and 10-year overall survival rates were 93% and 86% in the low-risk group and 95% and 91% in the intermediate-risk group (p > 0.05 by log-rank test). Five patients (0.3%) experienced grade 3 acute genitourinary (GU) toxicities, including urinary retention, hematuria, and frequency. 30 (2%) experienced grade 3 late GU toxicity, including urinary strictures, hematuria, and retention. One late grade 4 GU toxicity (hemorrhagic urethritis) and one late grade 4 gastrointestinal toxicity (fistula-in-ano) were seen. Conclusions: To the best of our knowledge, this is the largest analysis of long-term outcomes following SBRT for PCa. The results indicate that SBRT has an efficacy and toxicity profile that compares favorably to more widespread forms of treatment, such as conventionally-fractionated external beam radiotherapy and brachytherapy.

Abstract TP387: Abcd 2 Score Predicts The Long-term Risk Of Stroke After Transient Ischemic Attack: Fukuoka Stroke Registry

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Yasuhiro Kumai ◽  
Takuya Kiyohara ◽  
Masahiro Kamouchi ◽  
Sohei Yoshimura ◽  
Hiroshi Sugimori ◽  
...  
Keyword(s):  
High Risk ◽  
Transient Ischemic Attack ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Rank Test ◽  
Moderate Risk ◽  
Stroke Registry ◽  
Ischemic Attack

Background and Purpose— ABCD 2 score has been developed to predict the early risk of stroke after transient ischemic attack (TIA). The aim of this study was to clarify whether ABCD 2 score predicts the occurrence of stroke in the long term after TIA. Methods— Fukuoka Stroke Registry (FSR) is a multicenter epidemiological study database on acute stoke. From June 2007 to June 2011, 496 (305 males, 70 ± 13 years of age) patients who had suffered from TIA and were hospitalized in the 7 stroke centers within 7 days after the onset of TIA were enrolled in this study. The patients were divided into three groups according to the risk: low-risk (ABCD 2 score 0-3; n=72), moderate-risk (4-5; n=229) and high-risk group (6-7; n=195). They were followed up prospectively for up to 3 years. Cox proportional hazard regression model was used to elucidate whether ABCD 2 score was a predictor for stroke after TIA after adjusting for confounding factors. Results— Among three groups, there were significant differences in age, hypertension, diabetes mellitus and the decrease in estimated glomerular filtration rate (P<0.01, significantly). During a mean follow-up of 1.3 years, Kaplan-Meier analysis demonstrated that the stroke rate in TIA patients was significantly lower in low-risk group than in moderate-risk or high-risk group (log rank test, p<0.001). The adjusted hazard ratios for stroke in patients with TIA increased with moderate-risk group (Hazard ratio [HR]: 3.47, 95% CI: 1.03-21.66, P<0.05) and high-risk group (HR: 4.46, 95% CI: 1.31-27.85, P<0.05), compared to low-risk group. Conclusions— The ABCD 2 score is able to predict the long-term risk of stroke after TIA.

Long-term outcomes of endovascular aneurysm repair for challenging aortic necks using the Talent endograft

Vascular ◽  
2011 ◽  
Vol 19 (3) ◽  
pp. 132-140 ◽  
Author(s):  
Jeffrey Jim ◽  
Brian G Rubin ◽  
Patrick J Geraghty ◽  
Luis A Sanchez
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Endovascular Aneurysm Repair ◽  
High Risk Group ◽  
Low Risk ◽  
Long Term Results ◽  
Long Term Outcomes ◽  
Aneurysm Repair ◽  
Related Mortality

The aim of the present paper is to evaluate the long-term outcomes of endovascular aneurysm repair (EVAR) for challenging aortic necks. Subgroup analyses were performed on 156 patients from the prospective multicenter Talent eLPS (enhanced Low Profile Stent Graft System) trial. Patients with high-risk aortic necks (length < 15 mm or diameter ≥28 mm) were compared with the remaining patients. Patients with high-risk ( n = 86) and low-risk necks ( n = 70) had similar age and gender distribution. Despite similar prevalences of co-morbidities, the high-risk group had higher Society for Vascular Surgery scores. The high-risk group also had larger maximum aneurysm diameters (56.6 versus 53.0 mm, P < 0.02). There were lower freedoms from major adverse events (MAEs) for the high-risk group at 30 days (84.9 versus 95.7%; P < 0.04) and 365 days (73.4 versus 89.2%; P = 0.02). Effectiveness endpoints at 12 m showed no significant differences. Freedom from all-cause mortality at 30 days (96.5 versus 100%) and aneurysm-related mortality at 365 days (96.0 versus 100%) were similar. At five years, there were no differences in endoleaks or change in aneurysm diameter. All migrations occurred in the high-risk group. The five-year freedom from aneurysm-related mortality for the high- and low-risk groups was 93.2 and 100%, respectively. In conclusion, despite a higher rate of MAEs within the first year and higher migration rates at five years, EVAR in aneurysms with challenging aortic necks can be treated with acceptable long-term results.

Tailored Approaches for Refined Prognostication in Chronic Lymphocytic Leukemia Patients with Mutated Versus Unmutated Immunoglobulin Receptors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3199-3199
Author(s):  
Panagiotis Baliakas ◽  
Theodoros Moysiadis ◽  
Anastasia Hadzidimitriou ◽  
Aliki Xochelli ◽  
Mattias Mattsson ◽  
...  
Keyword(s):  
High Risk ◽  
Low Risk ◽  
Rank Test ◽  
P Value ◽  
Paired Comparisons ◽  
Intermediate Risk ◽  
Log Rank Test ◽  
Recurrent Mutations ◽  
Prognostic Indices ◽  
Very High

Abstract The classification of CLL patients according to the somatic hypermutation status (SHM) of the immunoglobulin heavy variable (IGHV) genes, namely mutated (M-CLL) versus unmutated (U-CLL), reflects fundamental differences in disease biology and clinical course. Realizing this, here we followed a compartmentalized approach and addressed the issue of prognostication separately for M-CLL and U-CLL. In a multi-institutional cohort of 2366 patients [M-CLL, n=1364 (58%); U-CLL, n=1002 (42%)] consolidated within ERIC, the European Initiative in CLL, we assessed the clinical impact of 'traditional' (age and clinical stage at the time of diagnosis, gender, CD38 expression, FISH detected abnormalities included in the Döhner hierarchical model of cytogenetic aberrations), and novel prognosticators (recurrent mutations within the TP53, SF3B1, NOTCH1, MYD88, and BIRC3 genes; IGHV gene usage; membership in stereotyped subsets) within M-CLL and U-CLL. Our statistical approach was based both on Cox regression models and recursive partitioning algorithms; internal validation was performed via bootstrapping procedures. Given the retrospective nature of our study, time-to-first-treatment (TTFT) was the primary endpoint. As expected, M-CLL exhibited significantly longer TTFT compared to U-CLL [median TTFT: not yet reached (M-CLL) vs 1.9 years (95% CI: 0.01-12.3 years, U-CLL), p<0.0001]. Advanced clinical stages (Binet B-C) were associated with shorter TTFT in both M-CLL and U-CLL; a significantly worse outcome was also identified for Binet C versus Binet B cases (p<0.0001). Binet A patients received our special focus, representing 90% and 67% of M-CLL and U-CLL studied cases, respectively. Amongst Binet A M-CLL cases, TP53 aberrations [TP53abs, deletions of chromosome 17p, del(17p) and/or TP53 mutations], stereotyped subset #2 membership and trisomy 12 were identified as equally adverse prognostic indicators [median TTFT: 5.5 (95% CI: 0.2-12.8), 4 (95% CI: 0.6-6.8) and 7.3 (95% CI: 0.7-13.4) years, respectively; p-value: non-significant when applying the log-rank test for all paired comparisons); of note, TP53abs were mutually exclusive with the other two features. Amongst Binet A U-CLL cases, TP53abs, SF3B1 mutations and deletion of chromosome 11q [del(11q)] had an overall similar adverse impact [median TTFT for TP53abs, SF3B1 mutations and del(11q): 1.8 (95% CI: 0.01-4.4), 2 (95% CI: 0.01-7.7) and 2.1 (95% CI: 0.01-8.1) years, respectively, p-value: non-significant when applying the log-rank test for all paired comparisons]. Within the remaining Binet A U-CLL cases [i.e. those lacking TP53abs and/or SF3B1 mutations and/or del(11q)], the only parameter associated with shorter TTFT was male gender (median TTFT: 3.5 years, 95% CI: 0.5-8.1 years). Based on these findings, we developed two prognostic indices for assessing TTFT tailored specifically to M-CLL and U-CLL, respectively. Within M-CLL (Figure 1A), 4 subgroups were identified: (i) very high risk: Binet C with identical 5- and 10-year treatment-probability (TP) of 92%; (ii) high risk: Binet B, 5y-TP and 10y-TP: 64% and 84%, respectively; (iii) intermediate risk: Binet A with one of the following: TP53abs or +12 or subset #2 membership, 5y-TP and 10y-TP: 40% and 55%, respectively; and (iv) low risk: Binet A nonTP53abs/+12/subset#2, 5y-TP and 10y-TP: 12% and 25%, respectively. Within U-CLL (Figure 1B), 5 subgroups were identified: (i) very high risk: Binet C with 5- and 10-year TP of 100%; (ii) high risk: Binet B, identical 5y-TP and 10y-TP: 90% and 100%, respectively; (iii) intermediate risk: Binet A with one of the following: TP53abs or SF3B1 mutations or del(11q), 5y-TP and 10y-TP: 78% and 98%, respectively; (v) low risk: Binet A, male nonTP53abs/SF3B1mut/del(11q), 5y-TP and 10y-TP: 65% and 85%, respectively and (iv) very low risk: Binet A, female nonTP53abs/SF3B1mut/del(11q), 5y-TP and 10y-TP: 45% and 65%, respectively. In conclusion, we identified clinicobiological parameters with distinct prognostic implications for M-CLL and U-CLL. These parameters were used in order to develop prognostic indices tailored to SHM status that were found capable of distinguishing subgroups with markedly different outcomes. We argue that such a compartmentalized approach may supersede previous attempts, thus overcoming the pronounced heterogeneity of CLL and optimizing prognostication. PB and TM contributed equally as first authors Figure 1 Figure 1. Disclosures Rosenquist: Gilead Sciences: Speakers Bureau.

scholarly journals Identification and Validation of a Novel Clinical Signature to Predict the Prognosis in Confirmed Coronavirus Disease 2019 Patients

2020 ◽  
Author(s):  
Shangrong Wu ◽  
Zhiguo Du ◽  
Sanying Shen ◽  
Bo Zhang ◽  
Hong Yang ◽  
...  
Keyword(s):  
Risk Model ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Risk Group ◽  
Test Group ◽  
Training Group ◽  
Low Risk ◽  
Rank Test ◽  
Log Rank Test ◽  
Disease Prognosis

Abstract Background Our aim in this study was to identify a prognostic biomarker to predict the disease prognosis and reduce the mortality rate of coronavirus disease 2019 (COVID-19), which has caused a worldwide pandemic. Methods COVID-19 patients were randomly divided into training and test groups. Univariate and multivariate Cox regression analyses were performed to identify the disease prognosis signature, which was selected to establish a risk model in the training group. The disease prognosis signature of COVID-19 was validated in the test group. Results The signature of COVID-19 was combined with the following 5 indicators: neutrophil count, lymphocyte count, procalcitonin, age, and C-reactive protein. The signature stratified patients into high- and low-risk groups with significantly relevant disease prognosis (log-rank test, P &lt; .001) in the training group. The survival analysis indicated that the high-risk group displayed substantially lower survival probability than the low-risk group (log-rank test, P &lt; .001). The area under the receiver operating characteristic (ROC) curve showed that the signature of COVID-19 displayed the highest predictive accuracy regarding disease prognosis, which was 0.955 in the training group and 0.945 in the test group. The ROC analysis of both groups demonstrated that the predictive ability of the signature surpassed the use of each of the 5 indicators alone. Conclusions The signature of COVID-19 presents a novel predictor and prognostic biomarker for closely monitoring patients and providing timely treatment for those who are severely or critically ill.

Rituximab Maintenance Treatment For a Maximum Of 5 Years In Follicular Lymphoma: Results Of The Randomized Phase III Trial SAKK 35/03

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 508-508 ◽  
Author(s):  
Christian J. Taverna ◽  
Giovanni Martinelli ◽  
Felicitas Hitz ◽  
Walter Mingrone ◽  
Thomas Pabst ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Disease Progression ◽  
Maintenance Treatment ◽  
Rank Test ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Log Rank Test ◽  
Grade 3 ◽  
Unacceptable Toxicity

Abstract Background Rituximab maintenance has been shown to be effective in patients with follicular lymphoma. The optimal duration of maintenance treatment remains unknown. Methods 270 patients (median age 57 years: range 25-82) with either untreated, relapsed, stable or chemotherapy resistant follicular lymphoma of all grades were treated with 4 weekly doses of rituximab monotherapy (375 mg/m²). Patients responding to the induction treatment (partial or complete response) received rituximab (375 mg/ m²) maintenance and were randomized either to a short maintenance consisting of four administrations every two months (arm A), or a prolonged maintenance for a maximum of five years or until disease progression or unacceptable toxicity (arm B). The primary endpoint was event-free survival (EFS) from randomization. Sample size calculation allowed detecting a median EFS increase with prolonged maintenance from 2.5 to 4.5 years with 80% power. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and objective response. Comparisons between the two treatment arms were performed using the log-rank test for survival endpoints. Results From October 2004 to November 2007 165 patients were randomized, 82 in arm A and 83 in arm B. 124 patients were chemotherapy-naïve. The median EFS is 3.4 years (95% CI 2.1-5.3) in arm A and 5.3 years (95% CI 3.5-NA) in arm B. Using the prespecified log-rank test this difference is statistically not significant (p=0.14). We observed an unexplained difference in disease progression and relapse during the first 8 months after randomization (3 in arm A vs. 10 in arm B) when treatment in both arms was the same which led to an early crossing of the EFS curves at 18 months. Considering only patients at risk after 8 months from randomization EFS in arm B is significantly prolonged compared to arm A (median EFS 7.1 (95% CI 4.4-NA) vs. 2.9 years (95% CI 1.8-4.8); log-rank test p=0.004). Median PFS is significantly longer in arm B (7.4 (95% CI 5.1-NA) vs. 3.5 years (95% CI 2.1-5.9); log-rank test p=0.04). There is no significant difference in OS and in the observed best response. Maintenance treatment was stopped due to unacceptable toxicity in no patient in arm A vs. 3 in arm B. Six subsequent cancers developed in arm A and 8 in arm B. One infection grade ≥3 was reported in arm A whereas seven infections grade ≥3 occurred in 5 patients in arm B. Conclusions EFS, the primary endpoint was not met which is mainly due to the early separation of the survival curves favouring arm A, at a time when the treatment in both arms was the same. However, a retrospectively defined analysis considering only EFS events from the time when treatment was different in the two arms, shows a statistically significant increase in EFS with long-term maintenance compared to the 8 months maintenance regimen. Long-term rituximab maintenance also doubles the median PFS without leading to increased undue toxicity. Disclosures: Off Label Use: Rituximab for 5 years. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Predicting mortality during long-term follow-up in pulmonary arterial hypertension

2021 ◽  
pp. 00837-2020
Author(s):  
David Kylhammar ◽  
Clara Hjalmarsson ◽  
Roger Hesselstrand ◽  
Kjell Jansson ◽  
Mohammad Kavianipour ◽  
...  
Keyword(s):  
Clinical Setting ◽  
Survival Rates ◽  
Real Life ◽  
Low Risk ◽  
Risk Assessments ◽  
Intermediate Risk ◽  
Long Term Follow Up ◽  
Pulmonary Arterial

The European Society of Cardiology (ESC) and European Respiratory Society (ERS) guideline recommendation of comprehensive risk assessments, which classify patients with pulmonary arterial hypertension (PAH) as having low, intermediate or high mortality risk, has not been evaluated during long-term follow-up in a “real-life” clinical setting. We therefore aimed to investigate the utility of risk assessment in a clinical setting for up to 5 years post diagnosis.Three hundred and eighty-six patients with PAH from the Swedish PAH Registry were included. Risk group (low/intermediate/high) and proportion of low risk variables were investigated at 3-, 4- and 5-year follow-ups after time of diagnosis. In an exploratory analysis, survival rates of patients with low- or high intermediate risk scores were compared.A low risk profile was in multivariate Cox proportional hazards regressions found to be a strong, independent predictor of longer transplant-free survival (p<0.001) at the 3-, 4- and 5-year follow-ups. Also, for the 3-, 4- and 5-year follow-ups, survival rates significantly differed (p<0.001) between the three risk groups. Patients with a greater proportion of low risk variables had better (p<0.001) survival rates. Patients with a high intermediate risk score had worse survival rates (p<0.001) than those with a low intermediate risk score. Results were similar when excluding patients with ≥3 risk factors for heart failure with preserved ejection fraction, atrial fibrillation and/or age >75 years at diagnosis.Our findings suggest that the ESC/ERS guideline strategy for comprehensive risk assessments in PAH is valid also during long-term follow-up in a “real-life” clinical setting.

scholarly journals Impact of Thromboembolism on Overall and Event-Free Survival in Children with Acute Lymphoblastic

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 51-52
Author(s):  
Marie-Claude Pelland-Marcotte ◽  
Ketan Kulkarni ◽  
Uma Athale ◽  
Jason Pole ◽  
Leonardo R. Brandao ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Diagnosis ◽  
Risk Group ◽  
Low Risk ◽  
Rank Test ◽  
Event Free Survival ◽  
Free Survival ◽  
Log Rank Test ◽  
Life Threatening ◽  
Very High

Introduction: Thromboembolism (TE) is a well-known complication of cancer and its treatments. The impact of TE on survival outcomes remains unclear, especially in children. We assessed whether TE development was associated with overall survival (OS) and event-free survival (EFS) in children with acute lymphoblastic leukemia (ALL). Methods: We performed a population-based retrospective cohort study using the national registry Cancer in Young People Canada (CYP-C). Children 0-&lt;15 years of age diagnosed with ALL (2000-2018) and treated at one of 12 Canadian pediatric centers outside of Ontario were included. OS was defined as the time between the date of cancer diagnosis and death and, EFS, as the time between the date of cancer diagnosis and the date of relapse, subsequent malignancy or death (whichever came first). Patients were categorized as to whether they experienced a radiologically-confirmed TE during treatment graded 3, 4 or 5 as per the Common Terminology Criteria for Adverse Events v.4 (i.e. requiring medical treatment, life-threatening or fatal). Only TEs that occurred before relapse or subsequent malignancy were considered. The Kaplan-Meier survival method estimated the 5-year OS and EFS of children with TE compared to those without TE. Univariate and multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of death or an event between groups, adjusted for age, sex, and leukemia risk group. A sub-analysis stratified the analysis by leukemia risk group. Results: The study included 2,208 children (median age: 4 years [interquartile range: 2-7 years], 54.9% male). Precursor B-cell ALL was the most common diagnosis (1,789, 89.1%). Patients were stratified as standard/low risk ALL in 58.0% of cases, and high/very high risk ALL in 42.0%. Of these, 121 (6.0%) developed a TE, at a median time of 100 days (interquartile range: 30-183 days) after cancer diagnosis. Eight patients (0.4%) had a life-threatening or fatal TE. Patients with TE were more likely to be aged 10 years or older, to present with T-cell ALL, and to have high risk leukemia. The 5-year OS (95% CI) of patients with and without TE was 80.2% (72.9-87.5%) and 93.7% (92.5-94.9%) respectively (log-rank test: p&lt;0.001, Figure 1). The adjusted HR (95% CI) of death in children with TE was 2.09 (1.33-3.27, p=0.001). Similarly, as shown in Figure 2, the 5-year EFS (95% CI) of patients with and without TE was 68.7% (59.7-77.7%) and 88.6% (87.1-90.1%), respectively (log-rank test: p&lt;0.001). The adjusted HR (95% CI) of an event was 2.01 (1.39-2.90, p&lt;0.001). When stratified by leukemia risk group, no statistically significant difference was seen in standard/low risk ALL for both OS and EFS but TE was associated with a significantly lower OS and EFS in children with high/very high risk ALL (Table 1). In this group, the increased risk of death was attributable to both deaths following relapsed disease (HR [95% CI]: 2.37 [1.39-4.04]) and death not following relapse (HR [95% CI]: 2.93 [1.35-6.35]). Sensitivity analyses in which 1) patients with very high risk ALL were removed and 2) only grade 3 or 4 TE were considered showed similar results. Conclusions: Clinically relevant TE led to a statistically significant reduction in OS and EFS in children with high risk/very high risk leukemia. Further research is needed to assess whether TE prevention may improve anti-cancer outcomes. Disclosures Brandao: Boehringer Ingelheim: Other: Member of a paediatric expert working group.

A Multicenter Phase II Study Of Bortezomib (VELCADE®) Combined With Rituximab For Untreated High Tumor Burden (HTB) Indolent Non-Hodgkin Lymphoma (NHL): Long-Term Follow-Up Of Outcomes and Examination Of Prognostic Factors

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1807-1807
Author(s):  
Andrew M Evens ◽  
Mitchell R Smith ◽  
Izidore S Lossos ◽  
Irene Helenowski ◽  
Michael Millenson ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Follicular Lymphoma ◽  
Phase Ii ◽  
Survival Rates ◽  
Cytotoxic Chemotherapy ◽  
Long Term Outcomes ◽  
Risk Of Death ◽  
Grade 3

Abstract Background Standard therapy for patients (pts) with untreated HTB indolent NHL includes rituximab combined with cytotoxic chemotherapy. There remains a deficiency of prospective data examining non-cytotoxic options. We examined long-term outcomes and prognostic factors for indolent NHL patients with HTB treated with front-line rituximab and bortezomib therapy. Methods We conducted a multicenter prospective phase II clinical trial for untreated indolent NHL pts (NCT 00369707). All pts were required to have HTB as defined by Groupe D’Etude des Lymphomes Folliculaires (GELF) criteria. Induction therapy consisted of 3 cycles of: rituximab at 375 mg/m2 x 4 weekly doses for cycle 1, then only day 1 for cycles 2 and 3 combined with bortezomib 1.6 mg/m2 days 1, 8, 15, and 22 given q35 days for all 3 cycles. This was followed by an abbreviated maintenance with both drugs given once q2 months x 8 months. Staging was done via CT with international workshop1999 criteria. All efficacy endpoints and survival rates were analyzed by intent-to-treat (ITT). Additionally, we examined prognostic factors for associations with survival on univariate analyses. Results 42 pts were enrolled and all pts were evaluable for toxicity and efficacy. Histologies were follicular lymphoma (FL) (n=33, 79%), marginal zone lymphoma (MZL) (n=6, 12%), small lymphocytic lymphoma (SLL) (n=2, 7%), and Waldenstroms (n=1, 2%). Median age was 62 years (40-86) with 21% of pts age >70 years; 91% of pts had advanced-stage disease (67% stage IV). Additional characteristics included: B symptoms in 31%, 38% with bulky disease (>7cm), and malignant ascites or effusions were present in 19%. The median FLIPI was 3 (61% were 3-5). Overall, therapy was well tolerated with minimal cytopenias noted. Most adverse events (AEs) occurred during the 3 induction cycles. Grade 3 AEs were: fever (5%), infusion reaction (5%), infection (5%), cardiac (5%), and fatigue (5%), as well as diarrhea, hypokalemia, and bowel obstruction each at 2%. The only grade 4 AEs were neutropenia (5%) and thrombocytopenia (2%); 3 pts were taken off study early (each after 1 cycle of induction) due to grade 3 diarrhea, fatigue, and cardiac AEs (latter due to CHF exacerbation, deemed unrelated to therapy [pt autonomously stopped cardiac medications]). Following the 3 induction cycles, the overall response rate (ORR) on ITT was 69% for all pts with a complete remission (CR) rate of 24% (FL ORR 70%, CR 23% on ITT). The ORR at end of therapy for all pts was 69% with 39% CR, while for FL, the end of therapy ORR was 75% and CR 44%. With a median follow-up of 48 months (10-78) and on ITT, the 4-year progression-free survival (PFS) for all pts was 44% with a 4-year overall survival (OS) rate of 87%. The 4-year PFS and OS rates for FL patients were 44% and 97%, respectively (Figure 1). Further, the 4-year OS rate for FL pts was significantly better compared with non-FL pts (97% (95% CI 80%, 99%) versus 43% (95% CI 6%, 78%), respectively, P=0.003). The time-to-treatment failure rate at 4 years for all pts was 26%, which was primarily due to the aforementioned AEs resulting in study removal and several non-progressing pts taken off study at physician discretion. Analyzing predictors of survival on univariate analysis, there was a trend for FLIPI to impact PFS of FL pts (HR: 1.48, 95% CI 0.95-2.32, P=0.08) as well as OS (HR: 3.34, 95% CI 0.89-12.56, P=0.08). Further, OS was similar, but PFS rates for FL pts were significantly different by low and high-risk FLIPI groups (Figure 2); 4-year PFS for FLIPI 0-2 was 57% (95% CI 29%, 77%) vs 28% (95% CI 8%, 53%) for FLIPI 3-5 (P=0.02). In addition, FL histology had a significant effect favoring lower risk of death vs non-FL histology (OS HR: 0.07, 95% CI 0.01-0.70, P=0.02). Conclusions In pts with untreated HTB NHL, therapy with rituximab/bortezomib was well tolerated and survival rates for FL pts approximated that of prior rituximab/cytotoxic chemotherapy series that have reported long-term outcomes of this pt population (e.g., R-CVP induction: Marcus R et al J Clin Oncol 2009). Moreover, OS for FL pts here was excellent, while OS for non-FL pts was sub-optimal. Continued strategies to incorporate novel therapeutic agents into frontline FL are warranted in part to delineate untreated HTB indolent NHL pt populations that may achieve long-term survival without use of cytotoxic therapy. Disclosures: Evens: Millennium: Consultancy, Honoraria. Off Label Use: Bortezomib in follicular lymphoma.

5-year outcomes from a prospective multi-institutional trial of heterogeneous dosing stereotactic body radiotherapy (SBRT) for low- and intermediate-risk prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 35-35 ◽  
Author(s):  
Donald B. Fuller ◽  
Brent L. Kane ◽  
Clinton A. Medbery ◽  
Kelly Underhill ◽  
James R. Gray ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Free Survival ◽  
High Dose Rate ◽  
Low Risk ◽  
High Dose ◽  
Intermediate Risk ◽  
Subsequent Decrease ◽  
Gu Toxicity

35 Background: SBRT is an emerging treatment for prostate cancer, but long-term reporting remains sparse. We present a prospective Phase II trial with 90% treated in community facilities. Methods: 14 institutions enrolled 259 patients - 112 low-risk; 147 intermediate-risk. The regimen emulated a high-dose rate brachytherapy (HDR) regimen - 38 Gy/4 fractions delivered by robotic SBRT. Androgen deprivation therapy was not allowed. HDR-like heterogeneous prostate dosing was used (Dmax >57 Gy). Toxicities were assessed by CTCAE v3.0 and quality of life assessed by Expanded Prostate Cancer Index Composite (EPIC). Biochemical recurrence was defined by Phoenix criteria. Results: Median follow-up is 5 years. 5-yr Grade 2 GU toxicity was 13.7% and GI toxicity 4.5%, with Grade 3 rates of 3% (GU) and 0% (GI) (one Gd 4 GU event). 5-yr median PSA was 0.1 ng/mL with further subsequent decrease (7 y = 0.035 ng/mL). 5-yr biochemical disease-free survival (bDFS) = 100% for low-risk and 88.5% for int-risk. 6 patients developed distant metastasis and one died of disease. Median EPIC GU obstruction and GI scores were similar at baseline vs. 5 years. 2% of patients had baseline GU incontinence requiring pad use vs 10% at 5 yrs. Of baseline potent men, 46% remained so at 5 yrs (66.7% for those age ≤65 vs. 37.1% age >65 at treatment). Conclusions: This is the first report of 5-year median follow-up outcomes post heterogeneous dosing SBRT for early prostate cancer. This treatment produces a low PSA nadir vs other forms of radiotherapy, with a favorable long-term result that appears reproducible in the community. Clinical trial information: 00643617. [Table: see text]

scholarly journals Radiomics and MGMT promoter methylation for prognostication of newly diagnosed glioblastoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Takahiro Sasaki ◽  
Manabu Kinoshita ◽  
Koji Fujita ◽  
Junya Fukai ◽  
Nobuhide Hayashi ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Accuracy ◽  
Risk Group ◽  
Prognostic Score ◽  
Methylation Status ◽  
Low Risk ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Log Rank Test ◽  
Newly Diagnosed Glioblastoma

Abstract We attempted to establish a magnetic resonance imaging (MRI)-based radiomic model for stratifying prognostic subgroups of newly diagnosed glioblastoma (GBM) patients and predicting O (6)-methylguanine-DNA methyltransferase promotor methylation (pMGMT-met) status of the tumor. Preoperative MRI scans from 201 newly diagnosed GBM patients were included in this study. A total of 489 texture features including the first-order feature, second-order features from 162 datasets, and location data from 182 datasets were collected. Supervised principal component analysis was used for prognostication and predictive modeling for pMGMT-met status was performed based on least absolute shrinkage and selection operator regression. 22 radiomic features that were correlated with prognosis were used to successfully stratify patients into high-risk and low-risk groups (p = 0.004, Log-rank test). The radiomic high- and low-risk stratification and pMGMT status were independent prognostic factors. As a matter of fact, predictive accuracy of the pMGMT methylation status was 67% when modeled by two significant radiomic features. A significant survival difference was observed among the combined high-risk group, combined intermediate-risk group (this group consists of radiomic low risk and pMGMT-unmet or radiomic high risk and pMGMT-met), and combined low-risk group (p = 0.0003, Log-rank test). Radiomics can be used to build a prognostic score for stratifying high- and low-risk GBM, which was an independent prognostic factor from pMGMT methylation status. On the other hand, predictive accuracy of the pMGMT methylation status by radiomic analysis was insufficient for practical use.

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