scholarly journals A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Sherise D Ferguson ◽  
Tiffany R Hodges ◽  
Nazanin K Majd ◽  
Kristin Alfaro-Munoz ◽  
Wajd N Al-Holou ◽  
...  

Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors. Methods A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas. Results Univariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden (P = .0055) and PTEN mutations (P = .0235) negatively impacted survival, whereas IDH1 mutations positively impacted survival (P < .0001). Clinical factors significantly associated with GBM survival included age (P < .0001), preoperative Karnofsky Performance Scale score (P = .0001), sex (P = .0164), and clinical trial participation (P < .0001). Higher preoperative T1-enhancing volume (P = .0497) was associated with shorter survival. The ratio of TI-enhancing to nonenhancing disease (T1/T2 ratio) also significantly impacted survival (P = .0022). Conclusions Our newly devised long-term survival-predictive nomogram based on clinical and genomic data can be used to advise patients regarding their potential outcomes and account for confounding factors in nonrandomized clinical trials.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248633
Author(s):  
Dirk Weyhe ◽  
Dennis Obonyo ◽  
Verena Nicole Uslar ◽  
Ingo Stricker ◽  
Andrea Tannapfel

Factors for overall survival after pancreatic ductal adenocarcinoma (PDAC) seem to be nodal status, chemotherapy administration, UICC staging, and resection margin. However, there is no consensus on the definition for tumor free resection margin. Therefore, univariate OS as well as multivariate long-term survival using cancer center data was analyzed with regards to two different resection margin definitions. Ninety-five patients met inclusion criteria (pancreatic head PDAC, R0/R1, no 30 days mortality). OS was analyzed in univariate analysis with respect to R-status, CRM (circumferential resection margin; positive: ≤1mm; negative: >1mm), nodal status, and chemotherapy administration. Long-term survival >36 months was modelled using multivariate logistic regression instead of Cox regression because the distribution function of the dependent data violated the requirements for the application of this test. Significant differences in OS were found regarding the R status (Median OS and 95%CI for R0: 29.8 months, 22.3–37.4; R1: 15.9 months, 9.2–22.7; p = 0.005), nodal status (pN0 = 34.7, 10.4–59.0; pN1 = 17.1, 11.5–22.8; p = 0.003), and chemotherapy (with CTx: 26.7, 20.4–33.0; without CTx: 9.7, 5.2–14.1; p < .001). OS according to CRM status differed on a clinically relevant level by about 12 months (CRM positive: 17.2 months, 11.5–23.0; CRM negative: 29.8 months, 18.6–41.1; p = 0.126). A multivariate model containing chemotherapy, nodal status, and CRM explained long-term survival (p = 0.008; correct prediction >70%). Chemotherapy, nodal status and resection margin according to UICC R status are univariate factors for OS after PDAC. In contrast, long-term survival seems to depend on wider resection margins than those used in UICC R classification. Therefore, standardized histopathological reporting (including resection margin size) should be agreed upon.


1997 ◽  
Vol 226 (2) ◽  
pp. 162-168 ◽  
Author(s):  
Yutaka Shimada ◽  
Masayuki Imamura ◽  
Ichio Shibagaki ◽  
Hisashi Tanaka ◽  
Tokiharu Miyahara ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4020-4020 ◽  
Author(s):  
Marianne Sinn ◽  
Bruno Valentin Sinn ◽  
Jana Kaethe Striefler ◽  
Jens Stieler ◽  
Marco Niedergethmann ◽  
...  

4020 Background: Long-term survival (LTS) in patients with pancreatic cancer is still rare, even in resectable and potentially curative stages. Few prospective data are available to identify predictive factors. The CONKO-001 study establishing adjuvant gemcitabine (GEM) may provide data to answer this question. Methods: CONKO-001 patients (pts) with an overall survival > 5 years were included in this analysis and compared to those with < 5 years. Central re-evaluation of the primary histology was done to confirm the diagnosis of pancreatic adenocarcinoma. Univariate analysis with the x²-test identified qualifying factors (p<0.10). Logistic regression with a stepwise selection process was used to investigate the influence of these covariates on LTS. Results: Of the 354 pts included in the intention-to-treat analysis of CONKO-001, 53 (15%) pts with an overall survival of more than 5 years could be identified, for 39 (74%) tumor specimens could be obtained. In 38 (97% of pts with LTS) the diagnosis of adenocarcinoma was confirmed, 1 showed a high-grade neuroendocrine tumor. Relevant factors for all 53 pts with LTS compared to remaining 301 non-LTS pts in univariate analysis were active treatment (GEM) (68% in LTS pts vs 48% in non-LTS pts; p=0.006), tumor grading (G1 17% vs 3%, G2 64% vs 55%, G3 17% vs 40%; p=0.000), tumor-size (T2 15% vs 9%, T3 74% vs 84%; p=0.004) and lymph nodes (N0 47% vs 25% N1 53% vs 74%; p=0.003. Significance could not be demonstrated for resection margin (R0 vs R1), sex, age, Karnofsky performance status (<80% vs 80% vs >80%) and CA 19-9 (40-100 U/ml vs <40 U/ml) at study entry. In the multivariate analysis tumor grading (gr) (odds ratio gr 3 vs gr 1=0.07; gr 3 vs gr 2= 0.38; p=0.017) and active treatment (odds ratio GEM vs observation=0.38; p=0.004) were the only independent prognostic factors. Conclusions: Long-term survival can be achieved in adenocarcinoma of the pancreas. In pts with completely resected pancreatic cancer, tumor grading and active treatment with GEM were the only predictive factor for LTS.


2011 ◽  
Vol 106 (3) ◽  
pp. 219-223 ◽  
Author(s):  
Andrew S. Barbas ◽  
Ryan S. Turley ◽  
Christopher R. Mantyh ◽  
John Migaly

2021 ◽  
Author(s):  
Manuel Artiles-Armas ◽  
Cristina Roque-Castellano ◽  
Roberto Fariña-Castro ◽  
Alicia Conde-Martel ◽  
María Asunción Acosta-Mérida ◽  
...  

Abstract Background: Frailty has been shown to be a good predictor of post-operative complications and death in patients undergoing gastrointestinal surgery. The aim of this study was to analyse the differences between frail and non-frail patients undergoing colorectal cancer surgery, as well as the impact of frailty on long-term survival in these patients.Methods: A cohort of 149 patients aged 70 years and older who underwent elective surgery for colorectal cancer was followed-up for at least 5 years. The sample was divided into two groups: frail and non-frail patients. The Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CSF) was used to detect frailty. The two groups were compared with regard to demographic data, comorbidities, functional and cognitive statuses, surgical risk, surgical variables, tumour extent, and post-operative outcomes, which were mortality at 30 days, 90 days and 1 year after the procedure. Univariate and multivariate analyses were also performed to determine which of the predictive variables were related to 5-year survival.Results: Out of the 149 patients, 96 (64.4%) were men and 53 (35.6) were women, with a median age of 75 years (IQR: 72-80). According to the CSHA-CSF scale, 59 patients (39.6%) were frail, and 90 patients (60.4%) were not frail. Frail patients were significantly older and had more impaired cognitive status, worse functional status, more comorbidities, more operative mortality, and more serious complications than non-frail patients. Comorbidities, as measured by the Charlson Comorbidity Index (p=0.001); the Lawton-Brody Index (p=0.011); failure to perform an anastomosis (p=0.024); nodal involvement (p=0.005); distant metastases (p<0.001); high TNM stage (p=0.004); and anastomosis dehiscence (p=0.013) were significant univariate predictors of a poor prognosis in univariate analysis. Multivariate analysis (Cox regression) of long-term survival, with adjustment for age, frailty, comorbidities and TNM stage, showed that comorbidities (p=0.002; HR:1.30; 95% CI:1.10–1.54) and TNM stage (p=0.014; HR:2.06; 95% CI:1.16-3.67) were the only independent risk factors for survival at five years.Conclusions: Frailty is associated with poor short-term post-operative outcomes, but it does not seem to affect long-term survival in patients with colorectal cancer. Instead, comorbidities and tumour stage are good predictors of long-term survival.


2021 ◽  
Author(s):  
Ryosuke Matsuda ◽  
Masatoshi Hasegawa ◽  
Tetsuro Tamamoto ◽  
Nobuyoshi Inooka ◽  
Mei Nikimoto ◽  
...  

Abstract Purpose: To evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). Methods: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. The tumors originated from the lung (n =189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). Results: The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40–100). The median follow-up time was 13 (range: 0–120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥80, and the absence of extracranial metastasis were associated with long-term survival. Conclusions: Female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.


1997 ◽  
Vol 15 (4) ◽  
pp. 1449-1454 ◽  
Author(s):  
C Bokemeyer ◽  
P Nowak ◽  
A Haupt ◽  
B Metzner ◽  
H Köhne ◽  
...  

PURPOSE Despite improved cure rates for patients with metastatic testicular cancer with cisplatin-based combination chemotherapy, patients who develop brain metastases are generally considered to possess a poor prognosis. This report summarizes the long-term results in 44 patients with brain metastases from testicular cancer treated between 1978 and 1995 at Hannover University Medical School. PATIENTS AND METHODS Histologically, 42 patients (95%) had a nonseminomatous germ cell cancer and two patients (5%) a seminoma. Thirty-nine patients (89%) had lung metastases and 37 (84%) fulfilled the criteria for advanced disease according to the Indiana University classification even without considering the brain metastases. Eighteen patients (41%) presented with brain metastases at primary diagnosis (group 1), four (9%) developed brain metastases at relapse after a previous favorable response to combination chemotherapy (group 2), and 22 (50%) developed brain metastases during or directly after cisplatin-based chemotherapy. Chemotherapy consisted of cisplatin-based combination treatment and radiotherapy was given as whole-brain irradiation of 30 to 40 Gy and in single cases combined with a boost of 10 Gy to single lesions. RESULTS Overall, 10 patients achieved long-term survival (23%; 95% confidence interval [CI], 10.1% to 35.4%). The prognosis was significantly better for patients in groups 1 and 2, with six of 18 (33%) and three of four (75%) patients alive, compared with only one of 22 (5%) in group 3 (P < .01). Patients treated with either chemotherapy or radiotherapy alone did not achieve long-term survival, while nine of 28 (32%) who received treatment with both modalities with or without surgery achieved sustained long-term survival. During univariate analysis, patients with the diagnosis of brain metastases at first presentation (P < .01), patients with a single brain lesion (P < .02), and patients who received combined chemotherapy and radiotherapy (P < .03) had a significantly improved outcome. CONCLUSIONS Long-term survival can be achieved in approximately 25% of patients with brain metastases from testicular cancer by combined treatment with brain irradiation and aggressive cisplatin-based chemotherapy. Patients who develop brain metastases during systemic treatment should receive only palliative radiation therapy, since sustained survival will not be reached.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17036-17036 ◽  
Author(s):  
S. Kim ◽  
H. Sohn ◽  
C. Suh ◽  
J. Ryu ◽  
E. Choi ◽  
...  

17036 Background: To investigate the role of weekly chemotherapy with paclitaxel/cisplatin and concurrent thoracic radiation (RT) as neoadjuvant therapy before surgical resection for patients with N2-IIIA NSCLC. Methods: Patients with pathologically proven N2 (pN2) and operable stage IIIA NSCLC were eligible. Six weekly chemotherapy with paclitaxel (50 mg/m2)/cisplatin (20 mg/m2) was given with concurrent thoracic RT (1.8 Gy/fraction once a day, 45 Gy) during 5 weeks. Chest CT, whole body PET were checked before and 3 weeks after chemoradiation. For the patients without clearing pN2 nodes or with pT3 after surgical resection, boost RT (20 Gy) was given. Results: From Jan. 2002 to Nov. 2005, 38 patients were enrolled. Median follow-up time was 20 months: gender (male: female, 30:8,), age (median 56, 42–67). Of them, 31 patients underwent surgical resection. Three patients showed brain metastasis during chmoradiation. Two patients refused surgical resection after chemoradiation. One patient showed severe radiation pneumonitis and was not fit for the operation. One patient showed lung to lung metastases before surgical resection. Of the 31 patients who underwent surgical resection, 14 (45.2%) showed pN0–1, and 7 (22.6%) showed pathologic complete remission (CR). Three year overall survival rate of all patients was 37.7% (median 35.9 months) and 3 year progression free survival was 34.2% (median 18 months). In univariate analysis, clearing N2 node and pathologic CR after surgery were the factors that could predict long-term survival. And the 2nd PET after chemoradiaiton could not expect clearing N2 nodes after surgical resection: sensitivity 44%, specificity 46%. As toxicities of WTP, hypersensivity reaction to paclitaxel and pneumonia with neutropenia were noted in 1 patient each. Severe radiation pneumonits was noted in 4 (of them 3 were given 65 Gy). Conclusions: WTP followed by surgical resection for N2-stage IIIA NSCLC was feasible. Clearing N2 nodes or pathologic CR after surgical resection were the factors of long-term survival. The usefulness of 2nd PET to expect the clearing N2 nodes was not adequate. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7555-7555
Author(s):  
S. Niho ◽  
K. Kubota ◽  
K. Yoh ◽  
K. Goto ◽  
H. Ohmatsu ◽  
...  

7555 Background: Our previous retrospective analysis demonstrated that the survival of the limited-disease (LD) SCLC pts with ipsilateral pleural effusion was intermediate between those of LD pts without ipsilateral pleural effusion and extensive-disease (ED) pts, and that long-term survival was achieved by LD-SCLC pts with ipsilateral pleural effusion who successfully underwent chemoradiotherapy (CRT) (J Thorac Oncol 2008;3:723–7). We retrospectively investigated the clinical course and outcome in pts with SCLC with pericardial effusion but no distant metastasis and examined the overall survival in pts who received chemotherapy and definitive thoracic radiotherapy (TRT). Methods: The medical records of SCLC pts who received treatment at the National Cancer Center Hospital East between July 1992 and December 2007 were reviewed. During this period 767 pts were newly diagnosed as having SCLC. Four-hundred seventeen pts had no distant metastasis. Ninety-six of those 417 pts (23%, 95% confidence interval (CI): 19–27%) had pleural or pericardial effusion or disseminated pleural nodules, and were included in this study. The 96 pts were divided into two groups: group A included pts with pericardial effusion (n=33), and group B included pts who had pleural effusion and/or disseminated pleural nodules, but did not have pericardial effusion (n=63). Sixteen pts had both pleural and pericardial effusion. Results: All but one patient received systemic chemotherapy. A remaining patient with pleural effusion received only best supportive care. In group A, 19 pts received chemoradiotherapy. TRT was conducted concurrently with 3 or 4 cycles of chemotherapy in 12 pts and sequentially in 7 pts. The response rate for first-line chemotherapy was 79%. In group B, 26 pts received chemoradiotherapy. Survival data were shown as below. Conclusions: Long-term survival was seldom achieved by SCLC pts with pericardial effusion but no distant metastasis, even if they underwent chemoradiotherapy. [Table: see text] No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11041-11041
Author(s):  
Florence Duffaud ◽  
Edouard Auclin ◽  
Antoine Italiano ◽  
Julien Mancini ◽  
Francois Bertucci ◽  
...  

11041 Background: A subset of metastatic GIST exhibit very long-term survival after imatinib (IM) introduction. The aim of this study was to analyse the clinico-biological characteristics of GIST pts alive > 10 years (yrs) after diagnosis (dx) of metastases (mets) and identify possible factors associated with long-term survival. Methods: Pts were identified from 2 sarcoma databases; NetSarc and ConticaGIST. Clinical data prospectively registered in the databases were supplemented with retrospective review of medical records. Results: We identified 141 pts (75 men, 66 women) with median age 54 (17-84) yrs and median ECOG 0 (0-2). Primary tumors (T) were all CD117+, and mainly gastric or intestinal (64 & 45 pts), with median size 10 (2-40) cm, CD34+ (82 pts), mitoses/50 HPF ≤ 5 (n = 36), or > 5 (n = 81). Genotype was documented in 82 (58%) pts with 73 (89%) KIT mutations (in exons 11,9 and 12 of 69, 3, and 1 pts respectively) and 9 WT KIT. 129 (91%) T were resected, 124 upfront, 5 post IM, with R0/R1/R2 resections in 61, 11, and 10 pts. Mets were mainly hepatic or peritoneal (78 & 51 respectively). 1st line TKI was given to 139 pts: 130 received IM; 88 (63%) within a clinical trial (CT), 41 (29%) had mets resection. Second, 3d and 4th line TKI were given to 81, 51 and 37 pts respectively, comprising 27, 7 and 10 from CT. Median number of TKIs was 2 (0-7), but 60 (44%) pts received only 1st line with no GIST progression within or after 10 yrs. 2 pts never received TKI but had mets resection. After median FU of 14.3 yrs (10-34.5), 104 remain alive, 37 died. Mean and Median OS from initial dx are 24 yrs (CI95% 21.6-27) and 20,8 yrs. Median PFS on TKIs are 127, 29, 21 and 22 mos on 1st, 2d, 3d and 4th line of TKI. In univariate analysis no factor is significantly associated with OS, but T size (≤ 10 vs > 10 cm) and oligometastatic disease (≤5 vs > 5 mets) are borderline significant (p = 0.056 and 0.07), and good PS (ECOG ≤ 1) at 2dline TKI initiation is associated with better PFS (p = 0.03). Conclusions: This large series of long-term ( > 10 yrs) survivors of metastatic GIST shows a high proportion of mets resection and a longer duration of PFS for TKI at any line. In this selected population, no prognostic factor is associated with long OS.


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