scholarly journals Clinical Predictors of Survival for Patients with Atypical Teratoid/Rhabdoid Tumors

2022 ◽  
Author(s):  
Vismaya S Bachu ◽  
Pavan Shah ◽  
Adrian E Jimenez ◽  
Adham M Khalafallah ◽  
Jignesh Tailor ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Bivariate Analysis ◽  
Cell Transplant ◽  
Clinical Predictors ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Abstract Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are malignant central nervous system (CNS) neoplasms of the young. Our study analyzed a large AT/RT cohort from the National Cancer Database (NCDB) to elucidate predictors of short-term mortality and overall survival (OS). Methods: Information was collected on patients with histologically-confirmed AT/RT using the NCDB (2004-2016). Kaplan-Meier analysis indicated OS. Prognostic factors for 30-day mortality, 90-day mortality, and OS were determined via multivariate Cox proportional-hazards (CPH) and logistic regression models. Results: Our cohort of 189 patients had a median age of 1 year (IQR [1, 4]) and tumor size of 4.7±2.0 cm at diagnosis. Seventy-two percent were under 3 years old; 55.6% were male and 71.0% were Caucasian. Fifty (27.2%) patients received only surgery (S) (OS=5.91 months), 51 (27.7%) received surgery and chemotherapy (S+CT) (OS=11.2 months), and 9 (4.89%) received surgery and radiotherapy (S+RT) (OS=10.3 months). Forty-five (24.5%) received S+CT+RT combination therapy (OS=45.4 months), 13 (17.1%) received S+CT+BMT/SCT (bone marrow or stem cell transplant) (OS=55.5 months), and 16 (8.70%) received S+CT+RT+BMT/SCT (OS=68.4 months). Bivariate analysis of dichotomized age (HR=0.550, 95% CI[0.357, 0.847], p=0.0067) demonstrated significantly increased patient survival if diagnosed at or above 1 year old. On multivariate analysis, administration of S+CT+RT, S+CT+BMT/SCT, or S+CT+RT+BMT/SCT combination therapy predicted significantly (p<0.05) increased OS compared to surgery alone. Conclusion: AT/RTs are CNS tumors where those diagnosed under 1 year old have a significantly worse prognosis. Our study demonstrates that while traditional CT, RT, and BMT/SCT combination regimens prolong life, overall survival in this population is still low.

Targeting of cyclin-dependent kinases in atypical teratoid rhabdoid tumors with multikinase inhibitor TG02

2021 ◽  
pp. 1-10
Author(s):  
Andy S. Ding ◽  
Sakibul Huq ◽  
Joshua Casaos ◽  
Divyaansh Raj ◽  
Manuel Morales ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Combination Therapy ◽  
Cell Viability ◽  
Cyclin D1 ◽  
Cell Counting ◽  
Cyclin Dependent Kinases ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

OBJECTIVE Atypical teratoid rhabdoid tumors (ATRTs) are aggressive pediatric brain tumors with no current standard of care and an estimated median patient survival of 12 to 18 months. Previous genetic analyses have implicated cyclin D1 and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase that is implicated in many cancers, as key drivers of tumorigenicity in ATRTs. Since the effects of EZH2 and cyclin D1 are facilitated by a host of cyclin-dependent kinases (CDKs), the authors sought to investigate the potential therapeutic effects of targeting CDKs in ATRTs with the multi–CDK inhibitor, TG02. METHODS Human ATRT cell lines BT12, BT37, CHLA05, and CHLA06 were selected for investigation. The effects of TG02 on cell viability, proliferation, clonogenicity, and apoptosis were assessed via Cell Counting Kit-8 assays, cell counting, clonogenic assays, and flow cytometry, respectively. Similar methods were used to determine the effects of TG02 combined with radiation therapy (RT) or cisplatin. Synergism indices for TG02-cisplatin combination therapy were calculated using CompuSyn software. RESULTS TG02 was observed to significantly impair ATRT cell growth in vitro by limiting cell proliferation and clonogenicity, and by inducing apoptosis. TG02 inhibited ATRT cell proliferation and decreased cell viability in a dose-dependent manner with nanomolar half maximal effective concentration (EC50) values (BT12, 207.0 nM; BT37, 127.8 nM; CHLA05, 29.7 nM; CHLA06, 18.7 nM). TG02 (150 nM) dramatically increased the proportion of apoptotic ATRT cells 72 hours posttreatment (TG02 8.50% vs control 1.52% apoptotic cells in BT12, p < 0.0001; TG02 70.07% vs control 15.36%, p < 0.0001). Combination therapy studies revealed that TG02 acted as a potent radiosensitizer in ATRT cells (BT12 surviving fraction, RT 51.2% vs RT + TG02 21.7%). Finally, CompuSyn analysis demonstrated that TG02 acted synergistically with cisplatin against ATRT cells at virtually all therapeutic doses. These findings were consistent in cell lines that cover all three molecular subgroups of ATRTs. CONCLUSIONS The results of this investigation have established that TG02 is an effective therapeutic against ATRTs in vitro. Given the lack of standard therapy for ATRTs, these findings help fill an unmet need and support further study of TG02 as a potential therapeutic option for patients with this deadly disease.

scholarly journals Elucidating the clinical-pathological factors and prognosis in breast cancer young surviving women who had a subsequent pregnant

2021 ◽  
Vol 2 (2) ◽  
pp. 013-025
Author(s):  
Ramírez-Torres Nicolás ◽  
Hernández-Valencia Marcelino ◽  
Rivas-Ruíz Rodolfo
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lymph Nodes ◽  
Proportional Hazards ◽  
Locally Advanced ◽  
Cox Proportional Hazards ◽  
Nodal Status ◽  
Bivariate Analysis ◽  
Risk Of Death ◽  
The Impact

Objective. To elucidate the impact of clinical-pathological factors on overall survival (OS) in patients who got pregnant after breast cancer treatment. Methods. Retrospective cohort of women age younger than 40 years with breast cancer history without active disease at diagnosis of postcancer pregnancy. Clinical-pathological factors were analized by age group and recent birth. Overall survival (OS) was evaluated from Kaplan-Meier method. The association between clinical-pathological factors and OS was examined using Cox proportional hazards method to estimate hazard ratio (HR) with 95% confidence intervals (CI). Results: A total of 14 patients were selected. Median age was 28.5 years (interquartile range, 26-35). Locally advanced stage (IIB-IIIB) was diagnosed in 64.3%. Patients lower than 35 years experienced more positive clinical lymph nodes (72.7%), grade 2 (63.6%) and ER/PgR-negative tumors (54.5% and 72.7%, respectively). The patients with ER-positive tumors showed an improvement non-significant at 5-year OS (87%; p = 0.097). In the bivariate analysis, patients with a higher number of pathological lymph nodes (pNs) had a 12% increase in the risk of death than those with lower number (HR = 1.12; 95% CI: 1.02 to 1.2). The multivariate model (after adjustment for number of pNs, age and tumor size) ascertained that the nodal status was the only independent predictor associated to a worse OS (HR = 1.15; 95% CI: 1.01 to 1.3). Conclusion. Pregnancy after cancer did not have a detrimental effect on survival. The patients < 35 years old group showed more unfavorable tumor features at diagnosis, which can largely explain a poorer prognosis. Nodal status was the most important prognostic factor that predicted the poor prognosis.

scholarly journals P11.23 Oncolytic adenovirus Delta-24-RGD exerts a potent anti-tumor effect in preclinical models of atypical teratoid/rhabdoid tumors

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii47-iii47
Author(s):  
M Garcia Moure ◽  
M González Huarriz ◽  
L Marrodán ◽  
A Patiño-García ◽  
M M Alonso
Keyword(s):  
Overall Survival ◽  
Brain Tumors ◽  
Phase I ◽  
Cell Lines ◽  
Pediatric Brain Tumors ◽  
Preclinical Models ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors ◽  
Pediatric Brain

Abstract BACKGROUND Atypical teratoid/rhabdoid tumors (AT/RTs) are rare pediatric brain tumors affecting mainly infants and young children. However, AT/RTs encompass almost 10% of death caused by pediatric brain tumors, and the 2-year overall survival for these children remains below 20%. For this reason, AT/RT ranks among the deadliest pediatric brain tumors. Therefore, it is clear we need to find out new therapeutic options for these children. Delta-24-RGD is an oncolytic adenovirus that has already demonstrated its efficacy as in Phase I/II clinical trials in adult patients affected by high grade gliomas with no evidence of severe side effects. Of interest for pediatric brain tumors, the safety of Delta-24-RGD is has also been demonstrated in an ongoing Phase I clinical trial for the treatment of DIPGs (NCT03178032). For these reasons, we propose to evaluate the anti-tumor effect of Delta-24-RGD in preclinical models of ATRT. MATERIAL AND METHODS Our studies have been carried out in three stablished AT/RT cell lines (BT-12, CHLA-06 and CHLA-266). In vitro, AT/RT cultures were infected with Delta-24-RGD-GFP to confirm the infectivity of the virus by flow cytometry. Replication of Delta-24-RGD was ensured by titrating the PFUs generated in AT/RT infected cultures. In regard to cytolytic effect, viability assays (MTS) were conducted in AT/RT cultures infected at increasing MOIs of Delta-24-RGD. In vivo, AT/RT cell lines were engrafted in Rag-2 mice in supratentorial and infratentorial locations, and the animals were treated with Delta-24-RGD at 107 or 108 PFU/animal (intra-tumor administration), or PBS. The therapeutic benefit of Delta-24-RGD was evaluated comparing the overall survival obtained for treated and untreated animals using the Log-rank test. We have also generated models of disseminated disease through intraventricular injection of the tumor cells, thus mimicking the lesions found in patients. AT/RT cell lines were transduced with a luc-expressing lentivirus to facilitate the follow up of these tumors. Mice bearing disseminated AT/RT were treated with Delta-24-RGD at 107 or 108 PFU/animal, or PBS (control). The therapeutic effect was monitored by bioluminescence and by comparison of the survival curves (Log-rank). RESULTS The virus was able to infect and replicate in tumor three different cell culture models of AT/RT, inducing a potent cytotoxic effect that resulting in IC50 values below 1 PFU/cell. Administration of the virus in mice bearing localized AT/RT (supratentorial and infratentorial) extended significantly the survival the animals, leading to up to 20% of long-term survivors. In disseminated AT/RT models, light emission reveals reduction of tumor growth in virus treated animals, resulting in an increased overall survival. CONCLUSION In conclusion, these results demonstrate that Delta-24-RGD could be a feasible therapeutic choice for patients affected by AT/RT.

scholarly journals Outcomes with respect to extent of surgical resection for pediatric atypical teratoid rhabdoid tumors

2019 ◽  
Vol 36 (4) ◽  
pp. 713-719
Author(s):  
Alexandra Richards ◽  
Ronak Ved ◽  
Christopher Murphy ◽  
Dawn Hennigan ◽  
John-Paul Kilday ◽  
...  
Keyword(s):  
Overall Survival ◽  
Surgical Resection ◽  
Total Resection ◽  
Term Survival ◽  
Common Location ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors ◽  
Extent Of Surgical Resection

Abstract Purpose To evaluate overall survival for atypical teratoid rhabdoid tumors (ATRTs) in relation to extent of surgical resection. Methods The neurosurgical tumor databases from three UK Pediatric centers (University Hospital of Wales, Alder Hey and Royal Manchester Children’s Hospital) were analyzed. Patients with a diagnosis of ATRT were identified between 2000 and 2018. Data was collected regarding demographics, extent of resection, complications, and overall survival. Results Twenty-four patients diagnosed with ATRT underwent thirty-eight operations. The age range was 20 days to 147 months (median 17.5 months). The most common location for the tumor was the posterior fossa (nine patients; 38%). Six patients (25%) underwent a complete total resection (CTR), seven (29%) underwent a near total resection (NTR), eight (33.3%) underwent a subtotal resection (STR), and three patients (12.5%) had biopsy only. Two-thirds of patients who underwent a CTR are still alive, as of March 2019, compared to 29% in the NTR and 12.5% in the STR groups. Out of the thirty-eight operations, there were a total of twenty-two complications, of which the most common was pseudomeningocele (27%). The extent of surgical resection (p = 0.021), age at surgery (p = 0.00015), and the presence of metastases at diagnosis (0.015) significantly affected overall survival. Conclusions Although these patients are a highly vulnerable group, maximal resection is recommended where possible, for the best chance of long-term survival. However, near total resections are likely beneficial when compared with subtotal resections and biopsy alone. Maximal surgical resection should be combined with adjuvant therapies for the best long-term outcomes.

Impact of Radiotherapy on Overall Survival in Children with Atypical Teratoid Rhabdoid Tumors

2009 ◽  
Vol 75 (3) ◽  
pp. S38-S39
Author(s):  
A.S. Pai Panandiker ◽  
C. Beltran ◽  
M. Naik ◽  
S. Sharma ◽  
A. Gajjar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

scholarly journals Survival rates and prognostic factors in right- and left-sided colon cancer stage I–IV: an unselected retrospective single-center trial

2021 ◽  
Author(s):  
Claudius E. Degro ◽  
Richard Strozynski ◽  
Florian N. Loch ◽  
Christian Schineis ◽  
Fiona Speichinger ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Blood Level ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Cancer Stage ◽  
Single Center ◽  
Significant Difference

Abstract Purpose Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods In total, 417 patients with colon cancer stage I–IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan–Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results Our study showed no significant difference of the overall survival between rCC and lCC stage I–IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1–123.5), CEA (carcinoembryonic antigen) blood level > 100 µg/l (HR: 3.3; CI 95%: 1.2–9.0), increased lymph node ratio of 0.6–1.0 (HR: 5.3; CI 95%: 1.7–16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7–2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9–91.9), CEA blood level 20.1–100 µg/l (HR: 5.4; CI 95%: 2.4–12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0–49.0), and severe surgical complications (Clavien-Dindo III–IV) (HR: 2.9; CI 95%: 1.5–5.5) were identified as predictors of a diminished overall survival. Conclusion Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients.

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