scholarly journals Radiogenomics-based Risk Prediction of Glioblastoma Multiforme with Clinical Relevance

2018 ◽  
Author(s):  
Xiaohua Qian ◽  
Hua Tan ◽  
Wei Chen ◽  
Weiling Zhao ◽  
Michael D. Chan ◽  
...  

AbstractGBM is the most common and aggressive primary brain tumor. Although the TMZ-based radiochemotherapy improves overall GBM patients’ survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudoprogression is a treatment-related reaction with an increase in contrast-enhancing lesion size at the tumor site or resection margins which mimics tumor recurrence on MRI. Accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed to develop a prognostic model to evaluate tumor progression potential of GBM patients following standard therapies. We applied a dictionary learning scheme to obtain imaging features of GBM patients with PsP or TTP from the Wake dataset. Based on these radiographic features, we then conducted radiogenomics analysis to identify the significantly associated genes. These significantly associated genes were then used as features to construct a 2YS logistic regression model. GBM patients were classified into low-and high-survival risk groups based on the individual 2YS scores derived from this model. We tested our model using an independent TCGA dataset and found that 2YS scores were significantly associated with the patients’ overall survival. We further used two cohorts of the TCGA data to train and test our model. Our results show that 2YS scores-based classification results from the training and testing TGCA datasets were significantly associated with the overall survival of patients. We also analyzed the survival prediction ability of other clinical factors (gender, age, KPS, normal cell ratio) and found that these factors were not related or weakly correlated with patients’ survival. Overall, our studies have demonstrated the effectiveness and robustness of the 2YS model in predicting clinical outcomes of GBM patients after standard therapies.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhihao Lv ◽  
Yuqi Liang ◽  
Huaxi Liu ◽  
Delong Mo

Abstract Background It remains controversial whether patients with Stage II colon cancer would benefit from chemotherapy after radical surgery. This study aims to assess the real effectiveness of chemotherapy in patients with stage II colon cancer undergoing radical surgery and to construct survival prediction models to predict the survival benefits of chemotherapy. Methods Data for stage II colon cancer patients with radical surgery were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (1:1) was performed according to receive or not receive chemotherapy. Competitive risk regression models were used to assess colon cancer cause-specific death (CSD) and non-colon cancer cause-specific death (NCSD). Survival prediction nomograms were constructed to predict overall survival (OS) and colon cancer cause-specific survival (CSS). The predictive abilities of the constructed models were evaluated by the concordance indexes (C-indexes) and calibration curves. Results A total of 25,110 patients were identified, 21.7% received chemotherapy, and 78.3% were without chemotherapy. A total of 10,916 patients were extracted after propensity score matching. The estimated 3-year overall survival rates of chemotherapy were 0.7% higher than non- chemotherapy. The estimated 5-year and 10-year overall survival rates of non-chemotherapy were 1.3 and 2.1% higher than chemotherapy, respectively. Survival prediction models showed good discrimination (the C-indexes between 0.582 and 0.757) and excellent calibration. Conclusions Chemotherapy improves the short-term (43 months) survival benefit of stage II colon cancer patients who received radical surgery. Survival prediction models can be used to predict OS and CSS of patients receiving chemotherapy as well as OS and CSS of patients not receiving chemotherapy and to make individualized treatment recommendations for stage II colon cancer patients who received radical surgery.


2020 ◽  
Vol 30 (6) ◽  
pp. 865-872 ◽  
Author(s):  
Cem Onal ◽  
Melis Gultekin ◽  
Ezgi Oymak ◽  
Ozan Cem Guler ◽  
Melek Tugce Yilmaz ◽  
...  

IntroductionData supporting stereotactic body radiotherapy for oligometastatic patients are increasing; however, the outcomes for gynecological cancer patients have yet to be fully explored. Our aim is to analyze the clinical outcomes of stereotactic body radiotherapy in the treatment of patients with recurrent or oligometastatic ovarian cancer or cervical cancer.MethodsThe clinical data of 29 patients (35 lesions) with oligometastatic cervical cancer (21 patients, 72%) and ovarian carcinoma (8 patients, 28%) who were treated with stereotactic body radiotherapy for metastatic sites were retrospectively evaluated. All patients had <5 metastases at diagnosis or during progression, and were treated with stereotactic body radiotherapy for oligometastatic disease. Patients with ≥5 metastases or with brain metastases and those who underwent re-irradiation for primary site were excluded. Age, progression time, mean biologically effective dose, and treatment response were compared for overall survival and progression-free survival.ResultsA total of 29 patients were included in the study. De novo oligometastatic disease was observed in 7 patients (24%), and 22 patients (76%) had oligoprogression. The median follow-up was 15.3 months (range 1.9–95.2). The 1 and 2 year overall survival rates were 85% and 62%, respectively, and the 1 and 2 year progression-free survival rates were 27% and 18%, respectively. The 1 and 2 year local control rates for all patients were 84% and 84%, respectively. All disease progressions were observed at a median time of 7.7 months (range 1.0–16.0) after the completion of stereotactic body radiotherapy. Patients with a complete response after stereotactic body radiotherapy for oligometastasis had a significantly higher 2 year overall survival and progression-free survival compared with their counterparts. In multivariate analysis, early progression (≤12 months) and complete response after stereotactic body radiotherapy for oligometastasis were the significant prognostic factors for improved overall survival. However, no significant factor was found for progression-free survival in the multivariable analysis. No patients experienced grade 3 or higher acute or late toxicities.ConclusionsPatients with early detection of oligometastasis (≤12 months) and with complete response observed at the stereotactic body radiotherapy site had a better survival compared with their counterparts. Stereotactic body radiotherapy at the oligometastatic site resulted in excellent local control rates with minimal toxicity, and can potentially contribute to long-term survival.


2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Li-Yeh Chuang ◽  
Guang-Yu Chen ◽  
Sin-Hua Moi ◽  
Fu Ou-Yang ◽  
Ming-Feng Hou ◽  
...  

Breast cancer is the most common cancer among women and is considered a major public health concern worldwide. Biogeography-based optimization (BBO) is a novel metaheuristic algorithm. This study analyzed the relationship between the clinicopathologic variables of breast cancer using Cox proportional hazard (PH) regression on the basis of the BBO algorithm. The dataset is prospectively maintained by the Division of Breast Surgery at Kaohsiung Medical University Hospital. A total of 1896 patients with breast cancer were included and tracked from 2005 to 2017. Fifteen general breast cancer clinicopathologic variables were collected. We used the BBO algorithm to select the clinicopathologic variables that could potentially contribute to predicting breast cancer prognosis. Subsequently, Cox PH regression analysis was used to demonstrate the association between overall survival and the selected clinicopathologic variables. C-statistics were used to test predictive accuracy and the concordance of various survival models. The BBO-selected clinicopathologic variables model obtained the highest C-statistic value (80%) for predicting the overall survival of patients with breast cancer. The selected clinicopathologic variables included tumor size (hazard ratio [HR] 2.372, p = 0.006), lymph node metastasis (HR 1.301, p = 0.038), lymphovascular invasion (HR 1.606, p = 0.096), perineural invasion (HR 1.546, p = 0.168), dermal invasion (HR 1.548, p = 0.028), total mastectomy (HR 1.633, p = 0.092), without hormone therapy (HR 2.178, p = 0.003), and without chemotherapy (HR 1.234, p = 0.491). This number was the minimum number of discriminators required for optimal discrimination in the breast cancer overall survival model with acceptable prediction ability. Therefore, on the basis of the clinicopathologic variables, the survival prediction model in this study could contribute to breast cancer follow-up and management.


2020 ◽  
Vol 2 (2) ◽  
pp. 71-85
Author(s):  
Isabel Novo ◽  
Bárbara Campos ◽  
Filipa Pinto-Ribeiro ◽  
Sandra F. Martins

Background: the presence of liver metastasis in colorectal cancer (CRC) remains one of the most significant prognostic factors. Objective: systematically review the results of studies evaluating the benefit of adding bevacizumab to a normal chemotherapy regime in the survival of patients with colorectal-cancer liver metastasis (CRLM). Search methods: Pubmed and Google Scholar databases were searched for eligible articles (from inception up to the 2 April 2019). Inclusion criteria: studies including patients with CRLM receiving anti-vascular endothelial growth factor (VEGF; bevacizumab) as treatment, overall survival as an outcome; regarding language restrictions, only articles in English were accepted. Main results: Eleven studies met the inclusion criteria. In 73% of these cases, chemotherapy with bevacizumab was an effective treatment modality for treating CRLM, and its administration significantly extended both overall survival (OS) and/or progression-free survival (PFS). Nevertheless, three articles showed no influence on survival rates of bevacizumab-associated chemotherapy. Author conclusions: It is necessary to standardize methodologies that aim to evaluate the impact of bevacizumab administration on the survival of patients with CRLM. Furthermore, follow-up time and the cause of a patient’s death should be recorded, specified, and cleared in order to better calculate the survival rate and provide a comparison between the produced literature.


2019 ◽  
Vol 29 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Cem Onal ◽  
Berna Akkus Yildirim ◽  
Sezin Yuce Sari ◽  
Guler Yavas ◽  
Melis Gultekin ◽  
...  

ObjectiveTo analyze the prognostic factors and treatment outcomes in endometrial cancer patients with paraaortic lymph node metastasis.MethodsData from four centers were collected retrospectively for 92 patients with endometrial cancer treated with combined radiotherapy and chemotherapy or adjuvant radiotherapy alone postoperatively, delivered by either the sandwich or sequential method. Prognostic factors affecting overall survival and progression-free survival were analyzed.ResultsThe 5-year overall survival and progression-free survival rates were 35 % and 33 %, respectively, after a median follow-up time of 33 months. The 5-year overall survival and progression-free survival rates were significantly higher in patients receiving radiotherapy and chemotherapy postoperatively compared with patients treated with adjuvant radiotherapy alone (P < 0.001 and P < 0.001, respectively). In a subgroup analysis of patients treated with adjuvant combined chemotherapy and radiotherapy, the 5-year overall survival and progression-free survival rates were significantly higher in patients receiving chemotherapy and radiotherapy via the sandwich method compared with patients treated with sequential chemotherapy and radiotherapy (P = 0.02 and P = 0.03, respectively). In the univariate analysis, in addition to treatment strategy, pathology, depth of myometrial invasion, and tumor grade were significant prognostic factors for both overall survival and progression-free survival. In the multivariate analysis, grade III disease, myometrial invasion greater than or equal to 50%, and adjuvant radiotherapy alone were negative predictors for both overall survival and progression-free survival.ConclusionWe demonstrated that adjuvant combined treatment including radiotherapyand chemotherapy significantly increases overall survival and progression-free survival rates compared with postoperative pelvic and paraaortic radiotherapy.


2005 ◽  
Vol 91 (4) ◽  
pp. 346-350 ◽  
Author(s):  
Nava Siegelmann-Danieli ◽  
Ofer Ben-lzhack ◽  
Alexandra Hanlon ◽  
John A Ridge ◽  
Moshe E Stein ◽  
...  

Aims and background The tumor suppressor gene P53 is mutated in almost half of head and neck cancers. The current work assessed the prognostic significance of P53 alteration in patients with squamous cell carcinoma of the oral tongue treated with a curative intent, its association with age at diagnosis (using 45 years as a cut point), and risk exposure as defined by tobacco and/or alcohol consumption. Methods P53 alteration was determined immunohistochemically in 45 patients with tongue cancer treated with a curative intent. Results P53 alteration occurred in 20 of 45 tumors (44%) and was more common among younger patients (58% versus 36% for younger versus older patients, respectively) and those lacking tobacco/alcohol exposure (53% versus 40% for “no-risk” and “risk” groups, respectively), but the differences were not statistically significant. With a median follow-up of 56 months, 5-year progression-free survival rates were 48% and 66% in patients with and without P53 detection, respectively (P = 0.22). Conclusions Despite a trend of a younger age at diagnosis in P53-altered tumors, results did not reach statistically significant differences. A trend of a worse clinical outcome with P53 alteration was noted.


2004 ◽  
Vol 22 (8) ◽  
pp. 1430-1438 ◽  
Author(s):  
E. Van Cutsem ◽  
H. van de Velde ◽  
P. Karasek ◽  
H. Oettle ◽  
W.L. Vervenne ◽  
...  

Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m2 intravenously weekly × 7 for 8 weeks, then weekly × 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade ≥ 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2030-2030
Author(s):  
Philip Bierman ◽  
Fausto Loberiza ◽  
Bhavana Dave ◽  
Warren Sanger ◽  
R. Gregory Bociek ◽  
...  

Abstract Rearrangements of the c-myc oncogene can be seen in 5–10% of patients with diffuse large B-cell lymphoma. However, studies examining the significance of this finding have yielded conflicting results. Therefore, we performed a retrospective analysis to determine the clinical significance of c-myc rearrangements in diffuse large B-cell lymphoma. The results of classical cytogenetic studies and FISH analyses were used to identify diffuse large B-cell lymphoma cases in the database of the Nebraska Lymphoma Study Group with or without c-myc rearrangements. Patients who were HIV positive and those with post-transplant lymphoproliferative disease were excluded. We identified 16 patients with diffuse large B-cell lymphoma and c-myc rearrangements. All patients were initially treated with doxorubicin- or mitoxantrone-containing chemotherapy regimens. The median age of these 16 patients was 61 years (range 40 to 80), and 5 (31%) were males. The International Prognostic Index (IPI) was 0–2 at diagnosis in 9 patients (56%), and 3–5 in 7 patients (44%). Eleven patients (69%) had bulky disease (≥ 5 cm) at diagnosis. No significant differences in outcome were identified when the 16 c-myc positive patients were compared with 97 c-myc negative diffuse large B-cell lymphoma patients in the same age range. The actuarial 5-year progression-free survival for the c-myc positive patients was 23% (95% CI 6% to 46%), as compared with 38% (95% CI 29% to 48%) for c-myc negative patients (p=0.17). The actuarial 5-year overall survival rates were 36% (95% CI 14% to 59%) and 47% (95% CI 36% to 56%), respectively (p=0.19). Classical cytogenetics and FISH analyses were also used to examine the 16 c-myc positive cases for bcl-2 rearrangements. Eight (50%) cases had rearrangements of bcl-2 in addition to c-myc rearrangements. These patients were similar to the c-myc positive/bcl-2 negative patients except for a higher likelihood of an elevated LDH level at diagnosis (88% vs. 25%; p=0.03). The actuarial 5-year progression-free survival for c-myc positive/bcl-2 positive patients was 0%, as compared to 33% (95% CI 6% to 66%) for patients with rearrangements of c-myc alone, and 37% (95% CI 28% to 47%) for c-myc negative patients. The actuarial 5-year overall survival rates were 12% (95% CI 1% to 42%), 47% (95% CI 12% to 76%), and 41% (95% CI 31% to 51%), respectively. A multivariate analysis, adjusting for IPI score, demonstrated that the relative risk (RR) of treatment failure was significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.86, 95% CI 1.32–6.23; p=0.008). Similarly, mortality was also significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.69, 95% CI 1.18–6.11; p=0.02). In contrast, no significant differences in treatment failure or overall survival were demonstrated when c-myc positive/bcl-2 negative patients were compared with c-myc negative patients. Our results demonstrate that the c-myc rearrangement is not associated with poorer survival in patients with diffuse large B-cell lymphoma. However, patients with rearrangements of bcl-2 in addition to c-myc had significantly worse progression-free survival and overall survival.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7502-7502 ◽  
Author(s):  
M. Dreyling ◽  
R. Forstpointner ◽  
M. Gramatzki ◽  
H. Böck ◽  
M. Hänel ◽  
...  

7502 Background: Rituximab (R) prolongs the progression-free survival (PFS) in patients with follicular lymphoma (FL) when given either simultaneously with or as maintenance after chemotherapy only. Methods: In the current study the impact of R maintenance after remission induction with an R-containing combined immuno-chemotherapy (R-FCM) was evaluated. Patients with advanced stage relapsed or refractory FL and mantle cell lymphoma (MCL) were eligible. The study design comprized 4 courses of chemotherapy with Fludarabine (25 mg/m2/d days 1–3), Cyclophosphamide (200 mg/m2/d days 1–3) and Mitoxantrone (8 mg/m2/d day 1) (FCM) ± Rituximab (375 mg/m2/d day 0). Patients entering a complete (CR) or partial remission (PR) underwent a second randomization for R maintenance (4 weekly doses (375 mg/m2/d) at three and nine months after end of induction) or observation only. Randomization was stratified for histology, prior therapies (up to 2 lines vs. >2), induction (±R), and response (CR vs. PR). After improved outcome of the R-FCM arm had been observed in the initial 147 randomized patients, all subsequent patients received a combined immuno-chemotherapy induction. Results: 176 of 195 randomized cases are evaluable, 138 of whom had received an R-containing induction. In these patients (as well as the total group) the median PFS after end of induction has not been reached in the R-maintenance arm in contrast to 17 months in patients with no further treatment (p = 0.001). This improvement was seen both in FL (n = 81; p = 0,035) and MCL (n = 47; p = 0,049). More importantly, overall survival rate was also improved after R maintenance with borderline significance (3 y rate 82% vs. 55%; p = 0,056). No major sided effects of R maintenance have been observed and the rate of serious infections was similar in both study arms (p = 0.72). Conclusions: The final analysis of this study confirms that R maintenance after combined immuno-chemotherapy (R-FCM) is highly effective and improves the progression-free survival—with a strong trend towards improved overall survival—of patients with relapsed FL and MCL. [Table: see text]


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 136-136
Author(s):  
Kyu-Hyoung Lim ◽  
Hui-Young Lee ◽  
Sung Bae Park ◽  
Seo-Young Song

136 Background: The combination chemotherapy of 5-fluorouracil (5-FU) and Oxaliplatin is usually used in gastric cancer (GC) and colorectal cancer (CRC). The safety and efficacy of the combination chemotherapy in patients over 80-years old has not been established yet. The purpose of this study was to assess the clinical outcomes and tolerability in the combination with 5-FU, leucovorin and oxaliplatin as first-line treatment in extremely elderly patients with GC or CRC. Methods: Eligibility included: 1) more than 80-years old, 2) metastatic gastric or colorectal cancer 3) chemotherapy-naive, 4) ECOG PS 0-1, 5) adequate organ function. Patients received the combination chemotherapy of 5-FU, leucovorin and oxaliplatin. Response evaluation was done every 8 weeks with RECIST criteria and toxicity was evaluated with NCI-CTCAE. Results: Between Sep 2008 and Nov 2014, 28 patients were reviewed and composed of equal numbers of GC and CRC. The median age was 82.2 years (80.0-85.6yrs) in GC and 81.1 years (80.0-89.3) in CRC, respectively. Total administrated cycles were 89 with median cycles of 5 in GC and 112 with median cycles of 11 in CRC. The median progression-free survival (PFS) and overall survival (OS) in GC were 5.4 months and 6.6 months, as compared with 7.3 months and 8.1 months, respectively. There were no significant difference in PFS (p = 0.94) and OS (p = 0.28) between GC and CRC. Overall survival rates at 1 year were 35.7% and 42.9%, respectively. After disease progression, salvage chemotherapy in GC and CRC was administrated in 1 and 7 patients, respectively. Common grade 3/4 hematology toxicities in both group were neutropenia, anemia. Frequent non-hematological toxicities were anorexia (60%), neuropathy (40%) and mucositis (25%), which were grade 1/2. Conclusions: The combination chemotherapy of 5-fluorouracil (5-FU) and Oxaliplatin has limited effect on improvement of OS in metastatic gastric or colorectal cancer patients more than age of 80. Further studies on the role of chemotherapy in these extremely elderly patients are needed.


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