Precision medicine: Clinical outcomes including long-term survival according to the pathway targeted and treatment period–The IMPACT study.

2018 ◽  
Vol 36 (18_suppl) ◽  
pp. LBA2553-LBA2553 ◽  
Author(s):  
Apostolia Maria Tsimberidou ◽  
David S. Hong ◽  
Jennifer J. Wheler ◽  
Gerald Steven Falchook ◽  
Aung Naing ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Single Agent ◽  
Pi3k Pathway ◽  
Molecular Testing ◽  
Term Survival ◽  
Starting Point ◽  
Long Term Follow Up ◽  
The Impact

LBA2553 Background: We evaluated the impact of pathway targeted and long-term follow-up of patients (pts) with refractory cancers referred to phase I trials. Methods: Pts referred to our program (2007-2013) had CLIA molecular testing. Pts treated with matched targeted therapy (MTT) vs. non-matched therapy (NMT) were analyzed. Results: Of 3,743 pts who had testing, 1,307 had ≥1 alteration and received therapy (MTT 711, NMT 596): med. age 57 yrs, range 16-86; 39% men; med. no. of prior therapies 4, range 0-16. The most common tumors were gastrointestinal 24.2%, gynecologic 19.4%, breast 13.5%, melanoma 11.9%, and lung 8.7%. Targeting MEK/RAF and RET pathways correlated with higher rates of CR/PR/SD≥6 months (mos), PFS and OS compared to others (all P < .001) (Table). Plateau was noted in OS (start, 38 mos): 74 of 711 (10.4%) in the MTT (max 10.7+ yrs) vs. 24 of 596 (4%) in the NMT (max 6 yrs) group were alive (p < .0001). In the MTT group, factors predicting longer PFS were non-PI3K pathway MTT (p < .001), no liver metastases (p < .001), PS < 2 (p = .006), normal LDH (p < .001) and albumin (p = .01) levels, and non-single agent therapy (p = .02). Factors predicting longer OS were non-PI3K pathway MTT (p < .001), no liver metastases (p < .001), PS < 2 (p < .001), normal LDH (p < .001) and albumin (p = .001) levels, and normal PLT counts (p = .03). Conclusions: Outcomes were superior in pts matched to RET and MEK/RAF inhibitors. Factors predicting longer PFS and OS were identified. In the MTT group, 10.4% of patients had OS ≥ 38 mos, the plateau starting point. Clinical trial information: NCT00851032. [Table: see text]

Cetuximab and chemotherapy in the treatment of patients with initially “nonresectable” colorectal (CRC) liver metastases: Long-term follow-up of the CELIM trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3538-3538 ◽  
Author(s):  
Gunnar Folprecht ◽  
Thomas Gruenberger ◽  
Wolf Bechstein ◽  
Hans-Rudolf Raab ◽  
Juergen Weitz ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Tumor Response ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Clinical Trial Information

3538 Background: CRC liver metastases can be resected after downsizing with intensive chemotherapy schedules, with a strong correlation between the response and resection rates. Cetuximab plus chemotherapy has been shown to increase the rates of tumor response and resection of liver metastases. (Van Cutsem et al, JCO 2011). Methods: Patients (pts) with technically non-resectable and/or with > 4 liver metastases were randomized to treatment with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated regarding resectability every 2 months. Resection was offered to all patients who became resectable during the study. K-ras and b-raf status were retrospectively evaluated. Data on tumor response and resection were reported earlier (Folprecht et al, Lancet Oncol 2010). Overall and progression free survival were analyzed in December 2012. Results: Between Dec 2004 and March 2008, 56 pts were randomized to arm A, 55 to arm B. For the current analysis, 109 pts were evaluable for overall survival (OS), and 106 patients for PFS. The median OS was 35.7 [95% CI: 27.2-44.2] months (arm A: 35.8 [28.1-43.6], arm B: 29.0 [16.0-41.9], HR 1.03 [0.66-1.61], p=0.9). The median PFS was 10.8 [9.3-12.2] months (Arm A: 11.2 [7.2-15.3], Arm B: 10.5 [8.9-12.2], HR 1.18 [0.79-1.74], p=0.4). Patients with R0 resection had a better OS (median: 53.9 [35.9-71.9] mo) than patients without R0 resection (27.3 [21.1-33.4] mo, p=0.002) and a better PFS (median 15.4 [11.4-19.5] and 8.9 [6.7-11.1] mo in R0 resected and not R0 resected pts, p<0.001). The 5 year survival in R0 resected patients is 46.2% [29.5-62.9%]. Conclusions: This study confirmed a favourable long term survival of patients with initially “nonresectable” CRC liver metastases treated in a multidisciplinary approach of neoadjuvant chemotherapy with cetuximab and subsequent metastasectomy in pts who became resectable. Clinical trial information: NCT00153998. [Table: see text]

scholarly journals Efficacy of Surgery for the Treatment of Gastric Cancer Liver Metastases: A Systematic Review of the Literature and Meta-Analysis of Prognostic Factors

2021 ◽  
Vol 10 (5) ◽  
pp. 1141
Author(s):  
Gianpaolo Marte ◽  
Andrea Tufo ◽  
Francesca Steccanella ◽  
Ester Marra ◽  
Piera Federico ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Prognostic Factors ◽  
Liver Metastases ◽  
Meta Analysis ◽  
Multidisciplinary Treatment ◽  
Review Of The Literature ◽  
Term Survival ◽  
The Impact

Background: In the last 10 years, the management of patients with gastric cancer liver metastases (GCLM) has changed from chemotherapy alone, towards a multidisciplinary treatment with liver surgery playing a leading role. The aim of this systematic review and meta-analysis is to assess the efficacy of hepatectomy for GCLM and to analyze the impact of related prognostic factors on long-term outcomes. Methods: The databases PubMed (Medline), EMBASE, and Google Scholar were searched for relevant articles from January 2010 to September 2020. We included prospective and retrospective studies that reported the outcomes after hepatectomy for GCLM. A systematic review of the literature and meta-analysis of prognostic factors was performed. Results: We included 40 studies, including 1573 participants who underwent hepatic resection for GCLM. Post-operative morbidity and 30-day mortality rates were 24.7% and 1.6%, respectively. One-year, 3-years, and 5-years overall survival (OS) were 72%, 37%, and 26%, respectively. The 1-year, 3-years, and 5-years disease-free survival (DFS) were 44%, 24%, and 22%, respectively. Well-moderately differentiated tumors, pT1–2 and pN0–1 adenocarcinoma, R0 resection, the presence of solitary metastasis, unilobar metastases, metachronous metastasis, and chemotherapy were all strongly positively associated to better OS and DFS. Conclusion: In the present study, we demonstrated that hepatectomy for GCLM is feasible and provides benefits in terms of long-term survival. Identification of patient subgroups that could benefit from surgical treatment is mandatory in a multidisciplinary setting.

scholarly journals Impact of Coronary Artery Disease and Diabetes Mellitus on the Long-Term Follow-Up in Patients after Retrograde Recanalization of the Femoropopliteal Arterial Region

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Joanna Wojtasik-Bakalarz ◽  
Zoltan Ruzsa ◽  
Tomasz Rakowski ◽  
Andreas Nyerges ◽  
Krzysztof Bartuś ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Of Death ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Artery Disease ◽  
The Impact

The most relevant comorbidities in patients with peripheral artery disease (PAD) are coronary artery disease (CAD) and diabetes mellitus (DM). However, data of long-term follow-up of patients with chronic total occlusion (CTO) are scarce. The aim of the study was to assess the impact of CAD and DM on long-term follow-up patients after superficial femoral artery (SFA) CTO retrograde recanalization. In this study, eighty-six patients with PAD with diagnosed CTO in the femoropopliteal region and at least one unsuccessful attempt of antegrade recanalization were enrolled in 2 clinical centers. Mean time of follow-up in all patients was 47.5 months (±40 months). Patients were divided into two groups depending on the presence of CAD (CAD group: n=45 vs. non-CAD group: n=41) and DM (DM group: n=50 vs. non-DM group: n=36). In long-term follow-up, major adverse peripheral events (MAPE) occurred in 66.6% of patients with CAD vs. 36.5% of patients without CAD and in 50% of patients with DM vs. 55% of non-DM subjects. There were no statistical differences in peripheral endpoints in both groups. However, there was a statistically significant difference in all-cause mortality: in the DM group, there were 6 deaths (12%) (P value = 0.038). To conclude, patients after retrograde recanalization, with coexisting CTO and DM, are at higher risk of death in long-term follow-up.

scholarly journals Concomitant tricuspid regurgitation severity and its secondary reduction determine long-term prognosis after transcatheter mitral valve edge-to-edge repair

2021 ◽  
Author(s):  
Martin Geyer ◽  
Karsten Keller ◽  
Kevin Bachmann ◽  
Sonja Born ◽  
Alexander R. Tamm ◽  
...  
Keyword(s):  
Tricuspid Regurgitation ◽  
Survival Data ◽  
Common Finding ◽  
Prognostic Impact ◽  
Term Survival ◽  
Long Term Prognosis ◽  
The Impact ◽  
Symptomatic Benefit

Abstract Background Concomitant tricuspid regurgitation (TR) is a common finding in mitral regurgitation (MR). Transcatheter repair (TMVR) is a favorable treatment option in patients at elevated surgical risk. To date, evidence on long-term prognosis and the prognostic impact of TR after TMVR is limited. Methods Long-term survival data of patients undergoing isolated edge-to-edge repair from June 2010 to March 2018 (combinations with other forms of TMVR or tricuspid valve therapy excluded) were analyzed in a retrospective monocentric study. TR severity was categorized and the impact of TR on survival was analysed. Results Overall, 606 patients [46.5% female, 56.4% functional MR (FMR)] were enrolled in this study. TR at baseline was categorized severe/medium/mild/no or trace in 23.2/34.3/36.3/6.3% of the cases. At 30-day follow-up, improvement of at least one TR-grade was documented in 34.9%. Severe TR at baseline was identified as predictor of 1-year survival [65.2% vs. 77.0%, p = 0.030; HR for death 1.68 (95% CI 1.12–2.54), p = 0.013] and in FMR-patients also regarding long-term prognosis [adjusted HR for long-term mortality 1.57 (95% CI 1.00–2.45), p = 0.049]. Missing post-interventional reduction of TR severity was predictive for poor prognosis, especially in the FMR-subgroup [1-year survival: 92.9% vs. 78.3%, p = 0.025; HR for death at 1-year follow-up 3.31 (95% CI 1.15–9.58), p = 0.027]. While BNP levels decreased in both subgroups, TR reduction was associated with improved symptomatic benefit (NYHA-class-reduction 78.6 vs. 65.9%, p = 0.021). Conclusion In this large study, both, severe TR at baseline as well as missing secondary reduction were predictive for impaired long-term prognosis, especially in patients with FMR etiology. TR reduction was associated with increased symptomatic benefit. Graphic abstract

scholarly journals Nontransplant therapy for bone marrow failure

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Danielle M. Townsley ◽  
Thomas Winkler
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Clonal Evolution ◽  
Single Agent ◽  
Telomere Attrition ◽  
Long Term Follow Up ◽  
Treatment Naïve

Abstract Nontransplant therapeutic options for acquired and constitutional aplastic anemia have significantly expanded during the last 5 years. In the future, transplant may be required less frequently. That trilineage hematologic responses could be achieved with the single agent eltrombopag in refractory aplastic anemia promotes new interest in growth factors after years of failed trials using other growth factor agents. Preliminary results adding eltrombopag to immunosuppressive therapy are promising, but long-term follow-up data evaluating clonal evolution rates are required before promoting its standard use in treatment-naive disease. Danazol, which is traditionally less preferred for treating cytopenias, is capable of preventing telomere attrition associated with hematologic responses in constitutional bone marrow failure resulting from telomere disease.

scholarly journals Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Graziamaria Corbi ◽  
Francesco Cacciatore ◽  
Klara Komici ◽  
Giuseppe Rengo ◽  
Dino Franco Vitale ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Cox Model ◽  
Survival Rates ◽  
Staging System ◽  
Female Gender ◽  
Term Survival ◽  
Fractional Polynomial ◽  
The Impact

AbstractAim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.

Abstract 5772: The Impact of Aortic Plaque Morphology on Survival Rate and the Incidence of Subsequent Embolic Event: Very Long-Term Follow-Up Data

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chisato Izumi ◽  
Shuichi Takahashi ◽  
Sumiyo Hashiwada ◽  
Koji Hanazawa ◽  
Jiro Sakamoto ◽  
...  
Keyword(s):  
Survival Rate ◽  
Event Rate ◽  
Plaque Morphology ◽  
Embolic Event ◽  
Aortic Plaque ◽  
Long Term Follow Up ◽  
The Impact ◽  
The Relationship

Atheromatous plaques of the aorta have been regarded as a potential source of emboli, but there are few reports about the frequency and prognosis of patients with thoracic aortic plaques and about the relationship between plaque morphology and prognosis, especially long-term follow-up data. The purpose of this study is to clarify the impact of aortic atheromatous plaque morphology on survival rate and the incidence of subsequent embolic event. We retrospectively investigated 1570 consecutive patients who underwent transesophageal echocardiography between 1991 and 2003. The presence of severe plaque (>5mm in thickness) in the thoracic aorta were examined. Survival rate and subsequent embolic event rate were compared between patients with severe plaque and 109 control patients. The control patients were selected from the patients who showed no or mild plaque and as they were matched for age, gender, and risk factors of atherosclerosis with the patients with severe aortic plaque. The relationship between aortic plaque morphology and prognosis was also estimated, according to the presence of ulceration, calcification, hypoechoic plaques, and mobile plaques. Mean follow-up period was 8.7 years. Among 1570 patients, severe aortic plaque was detected in 92 patients (5.9%). These 92 patients showed significantly low survival rate and high subsequent embolic event rate compared with control patients (8-year survival rate, 50% vs 87%, 8-year embolic event free rate, 57% vs 90%). The relative risk of death was significantly increased for ulceration (2.4, 95% CI;1.1–5.2) and the relative risk of embolic events was significantly increased for mobile plaques (2.2, 95% CI;1.1–5.1). In conclusion, aortic plaque > 5mm in thickness was a predictor of a low survival rate and a high embolic event rate. Among patients with aortic plaque >5mm in thickness, ulceration was a predictor of a low survival rate and mobile plaque was a predictor of a high embolic event rate.

Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1997 ◽  
Vol 15 (7) ◽  
pp. 2564-2569 ◽  
Author(s):  
S B Saxman ◽  
K J Propert ◽  
L H Einhorn ◽  
E D Crawford ◽  
I Tannock ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Intergroup Trial ◽  
Advanced Urothelial Carcinoma

PURPOSE A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. PATIENTS AND METHODS Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. RESULTS With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. CONCLUSION Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

The Different Impacts on the Long-Term Survival of Tunneled Internal Jugular Hemodialysis Catheters Based on Tip Position and Laterality

2017 ◽  
Vol 43 (4) ◽  
pp. 315-320 ◽  
Author(s):  
Vedran Premuzic ◽  
Drazen Perkov ◽  
Ranko Smiljanic ◽  
Bruna Brunetta Gavranic ◽  
Bojan Jelakovic
Keyword(s):  
Superior Vena ◽  
Vena Cava ◽  
The Body ◽  
Term Survival ◽  
Catheter Tip ◽  
Tip Position ◽  
The Impact

Background/Aims: The aim of this study was to examine the impact of different catheter tip positions on the life of the catheter, dysfunction, infection, and quality of hemodialysis and possible differences between the access site laterality in jugular-tunneled hemodialysis catheters. Methods: Catheters were evaluated for the following parameters: place of insertion, time of insertion, duration of use, and reason for removal. In all patients, the catheter tip position was checked using an X-ray. Results: The mean duration of implanted catheters with the tip placed in the cavo-atrial junction and right atrium was significantly longer. There were no differences in catheter functionality at follow-up or complications based on catheter laterality for each catheter tip position. Conclusion: According to our results, the localization of the catheter tip in superior vena cava still remains the least preferable method. Our results showed that the main factor responsible for better catheter functionality was not laterality but the depth to which the catheter tip is inserted into the body.

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