scholarly journals A Nomogram Predicting Progression Free Survival in Patients with Gastrointestinal Stromal Tumor Receiving Sunitinib: Incorporating Pre-Treatment and Post-Treatment Parameters

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2587
Author(s):  
Yau-Ren Chang ◽  
Wen-Kuan Huang ◽  
Shang-Yu Wang ◽  
Chiao-En Wu ◽  
Jen-Shi Chen ◽  
...  

The present study aimed to construct a prognostic nomogram incorporating pre-treatment and post-treatment factors to predict progression-free survival (PFS) after use of sunitinib in patients with metastatic gastrointestinal stromal tumors (GISTs) following imatinib intolerance or failure. From 2007 to 2018, 109 metastatic GIST patients receiving sunitinib at Chang Gung Memorial Hospital, Taiwan, were enrolled. A prognostic nomogram to predict PFS was developed. Sixty-three male and forty-six female metastatic GIST patients, with a median age of 61 years (range: 15–91 years), received sunitinib. The median PFS for 109 patients is 9.93 months. For pre-treatment factors, male gender, body mass index more than 18.5 kg/m2, no sarcopenia status, higher lymphocyte count, lower platelet/lymphocyte ratio, good performance status, higher sunitinib dose, and non-liver metastasis were significantly associated with favorable PFS. For post-treatment factors, adverse events with hypertension, hand–foot skin reaction, and diarrhea were significantly associated with favorable PFS. However, only eight clinicopathological independent factors for PFS prediction were selected for prognostic nomogram establishment. The calibration curve for probability of PFS revealed good agreement between the nomogram prediction and actual observation. High risk patients will experience the lowest PFS. A prognostic nomogram integrating eight clinicopathological factors was constructed to assist prognostic prediction for individual patients with advanced GIST after sunitinib use.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5003-5003
Author(s):  
Evan Y. Yu ◽  
Fenghai Duan ◽  
Mark Muzi ◽  
Jeremy Gorelick ◽  
Bennett Chin ◽  
...  

5003 Background: Dasatinib is a SRC kinase inhibitor that decreases bone turnover in men with metastatic castration-resistant prostate cancer (mCRPC). 18F-fluoride PET was used to evaluate differential response between normal and tumor bone to dasatinib. Methods: Patients with bone mCRPC underwent dynamic 18F-flouride PET imaging prior to and 12 weeks after dasatinib treatment. Up to 5 bone metastases with matching normal bone regions were selected for analysis by SUVmax, Ki, K1and Patlak flux. Their pre-treatment values and change from pre-treatment to post-treatment values were evaluated via generalized estimating equations to predict skeletal-related events (SRE) and via Cox proportional hazards modeling to predict progression-free survival (PFS) with Prostate Cancer Working Group 2 criteria, overall survival and time to SRE. Results: Eighteen patients treated with dasatinib underwent baseline 18F-flouride PET imaging; 12 had follow-up scans allowing assessment of changes due to therapy. Median age for all patients was 69 (range 48-86) years. Significant decrease in SUVmax (p=0.0002) occurred in bone metastases with dasatinib while significant increases in Patlak flux (p=0.0033) occurred in normal bone. Significant differences in changes from tumor bone compared to normal bone in response to dasatinib were noted for SUVmax (p<0.0001). Of 18 patients, 17 have either met progression criteria or death by the time of this analysis. Decrease in tumor bone SUVmax (p=0.019), Ki(p=0.022), and Patlak flux (p=0.034) from pre-treatment to post-treatment correlates with longer PFS. Conclusions: 18F-fluoride PET indicates differential effect of dasatinib on tumor compared to normal bone in men with mCRPC. In patients undergoing pre- and post-dasatinib 18F-fluoride PET imaging a decrease in bone mCRPC fluoride uptake in response to treatment correlates with PFS. Clinical trial information: NCT00936975.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20513-e20513
Author(s):  
Hongge Liang ◽  
Di Ma ◽  
Yan Xu ◽  
Jing Zhao ◽  
Minjiang Chen ◽  
...  

e20513 Background: We performed a retrospective analysis to investigate the association between the lactate dehydrogenase (LDH) levels and progression-free survival (PFS) in patients with echinoderm microtubule-associated protein-like 4-anaplasticlymphoma kinase (EML4-ALK) rearrangement non-small cell lung cancer (NSCLC) receiving treatment with crizotinib. Methods: Advanced NSCLC patients with EML4-ALK rearrangement receiving treatment with crizotinib were enrolled at Peking Union Medical College and Cancer Hospital Chinese Academy of Medical Sciences between January 2007 and January 2016. Pre-treatment or post-treatment serum LDH levels were analyzed with progression-free survival (PFS) and patients’ clinical parameters. Results: Overall, 212 patients were studied. Kaplan-Meier univariate analysis showed that elevated pre-treatment LDH level (7.9 vs. 14.1 months, P = 0.004) were associated with PFS, while the mean value of post-treatment LDH level (14.3 vs. 13.3 months, P = 0.970) were not associated with PFS. Coxproportional hazards model also identified that pre-treatment LDH level (hazard ratio [HR] = 1.841, 95% confidence interval [CI] 1.062-3.190, P = 0.030) was associated with the PFS. Logistic regression analysis showed that post-treatment LDH level was associated with creatine kinase(OR = 6.712, 95% CI 3.395-13.273, P < 0.01), CKMB (OR = 6.297, 95% CI 2.953-13.427, P < 0.01), and hemoglobin(OR = 4.163, 1.741-9.956, P = 0.001). Conclusions: An elevated pre-treatment serum LDH level ( > 250U/L) is significantly associated with shorter PFS in patients with EML4-ALK rearrangement NSCLC. Post-treatment elevated serum LDH level is associated with multiple factors including muscle damage and anemia, rather than PFS.


2020 ◽  
Vol 20 (11) ◽  
pp. 887-895 ◽  
Author(s):  
Martina Catalano ◽  
Giandomenico Roviello ◽  
Raffaele Conca ◽  
Alberto D’Angelo ◽  
Valeria Emma Palmieri ◽  
...  

Background: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice. Methods: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. Results: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. Conclusions: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.


2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.


2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


1986 ◽  
Vol 4 (6) ◽  
pp. 965-971 ◽  
Author(s):  
P F Conte ◽  
M Bruzzone ◽  
S Chiara ◽  
M R Sertoli ◽  
M G Daga ◽  
...  

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.


2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Hina Saeed ◽  
David M. King ◽  
Candice A. Johnstone ◽  
John A. Charlson ◽  
Donald A. Hackbarth ◽  
...  

Background. The management for unplanned excision (UE) of soft tissue sarcomas (STS) has not been established. In this study, we compare outcomes of UE versus planned excision (PE) and determine an optimal treatment for UE in STS.Methods. From 2000 to 2014 a review was performed on all patients treated with localized STS. Clinical outcomes including local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) were evaluated using the Kaplan-Meier estimate. Univariate (UVA) and multivariate (MVA) analyses were performed to determine prognostic variables. For MVA, Cox proportional hazards model was used.Results. 245 patients were included in the analysis. 14% underwent UE. Median follow-up was 2.8 years. The LR rate was 8.6%. The LR rate in UE was 35% versus 4.2% in PE patients (p<0.0001). 2-year PFS in UE versus PE patients was 4.2 years and 9.3 years, respectively (p=0.08). Preoperative radiation (RT) (p=0.01) and use of any RT for UE (p=0.003) led to improved PFS. On MVA, preoperative RT (p=0.04) and performance status (p=0.01) led to improved PFS.Conclusions. UEs led to decreased LC and PFS versus PE in patients with STS. The use of preoperative RT followed by reexcision improved LC and PFS in patients who had UE of their STS.


2018 ◽  
Vol 36 (25) ◽  
pp. 2585-2592 ◽  
Author(s):  
Cesare Gridelli ◽  
Alessandro Morabito ◽  
Luigi Cavanna ◽  
Andrea Luciani ◽  
Paolo Maione ◽  
...  

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.


Sign in / Sign up

Export Citation Format

Share Document