scholarly journals TERT promoter mutation and chromosome 6 loss define a high-risk subtype of ependymoma evolving from posterior fossa subependymoma

2021 ◽  
Author(s):  
Christian Thomas ◽  
Felix Thierfelder ◽  
Malte Träger ◽  
Patrick Soschinski ◽  
Michael Müther ◽  
...  
Keyword(s):  
Posterior Fossa ◽  
Progression Free Survival ◽  
Biological Behavior ◽  
Benign Tumors ◽  
Tumor Evolution ◽  
Free Survival ◽  
Molecular Group ◽  
Methylome Analysis ◽  
Mixed Tumors

AbstractSubependymomas are benign tumors characteristically encountered in the posterior fossa of adults that show distinct epigenetic profiles assigned to the molecular group “subependymoma, posterior fossa” (PFSE) of the recently established DNA methylation-based classification of central nervous system tumors. In contrast, most posterior fossa ependymomas exhibit a more aggressive biological behavior and are allocated to the molecular subgroups PFA or PFB. A subset of ependymomas shows epigenetic similarities with subependymomas, but the precise biology of these tumors and their potential relationships remain unknown. We therefore set out to characterize epigenetic traits, mutational profiles, and clinical outcomes of 50 posterior fossa ependymal tumors of the PFSE group. On histo-morphology, these tumors comprised 12 ependymomas, 14 subependymomas and 24 tumors with mixed ependymoma–subependymoma morphology. Mixed ependymoma–subependymoma tumors varied in their extent of ependymoma differentiation (2–95%) but consistently exhibited global epigenetic profiles of the PFSE group. Selective methylome analysis of microdissected tumor components revealed CpG signatures in mixed tumors that coalesce with their pure counterparts. Loss of chr6 (20/50 cases), as well as TERT mutations (21/50 cases), were frequent events enriched in tumors with pure ependymoma morphology (p < 0.001) and confined to areas with ependymoma differentiation in mixed tumors. Clinically, pure ependymoma phenotype, chr6 loss, and TERT mutations were associated with shorter progression-free survival (each p < 0.001). In conclusion, our results suggest that subependymomas may acquire genetic and epigenetic changes throughout tumor evolution giving rise to subclones with ependymoma morphology (resulting in mixed tumors) that eventually overpopulate the subependymoma component (pure PFSE ependymomas).

Posterior fossa meningiomas: perioperative predictors of extent of resection, overall survival and progression-free survival

2019 ◽  
Vol 161 (5) ◽  
pp. 1003-1011 ◽  
Author(s):  
Marco V. Corniola ◽  
Jean-Michel Lemée ◽  
Michele Da Broi ◽  
Holger Joswig ◽  
Karl Schaller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Posterior Fossa ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Free Survival

A phase II, multicenter study of encorafenib/binimetinib followed by a rational triple-combination after progression in patients with advanced BRAF V600-mutated melanoma (LOGIC2).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10022-10022 ◽  
Author(s):  
Reinhard Dummer ◽  
Shahneen Kaur Sandhu ◽  
Wilson H. Miller ◽  
Marcus O. Butler ◽  
Christian U. Blank ◽  
...  
Keyword(s):  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Tumor Evolution ◽  
Free Survival ◽  
Group A ◽  
The Individual ◽  
Bayesian Logistic Regression ◽  
Gene Alterations

10022 Background: LOGIC2 evaluates the benefit of a 3rd agent added to encorafenib (enco)/binimetinib (bini), selected at progression based on the genetic tumor evolution. Methods: In part I/run-In, pts were treated with enco/bini until disease progression (as defined per RECIST v1.1). Foundation One NGS was applied on a baseline sample and on a PD sample. Based on the genetic evolution between the biopsy at inclusion (bxI) and at progression (bxPD) and clinical considerations, pts entered part II and received one of four 3rd agent additions to enco/bini combinations: A. LEE011 (CDK4/6 inhibitor), B. BKM120 (PI3K inhibitor), C. INC280 (c-Met inhibitor), or D. BGJ398 (FGFR inhibitor). An adaptive Bayesian logistic regression model (BLRM) guided by the escalation with overdose control (EWOC) principle was used to make dose escalation decisions. Assessments include objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. Data cutoff for this analysis was May 12, 2019. Data is as is. Part 1 of study is ongoing. Part 2 of study is closed to enrollment. Results: 58 pts enrolled into part II (group A=38; B=6; C=13; D=1). 29 pts were assigned to treatment based on bxPD results (Table). In groups A, B, and C, the confirmed ORR was 5.3%, 0%, and 0%, and the DCR was 26.3%, 16.7%, and 15.4%, with median PFS of 2.1, 1.6, and 2.2 months, respectively. Safety was consistent with known profiles of the individual agents. Conclusions: Triple therapy is feasible when a 3rd agent is added to enco/bini at progression based on genetic alterations, although activity observed was low. Further exploration to identify patterns of resistance susceptible to the addition of a 3rd agent is needed. Gene alterations for enrollment into part 2. Clinical trial information: NCT02159066. [Table: see text]

scholarly journals Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

2013 ◽  
Vol 21 (3) ◽  
pp. R105-R120 ◽  
Author(s):  
Louis de Mestier ◽  
Clarisse Dromain ◽  
Gaspard d'Assignies ◽  
Jean-Yves Scoazec ◽  
Nathalie Lassau ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Targeted Therapies ◽  
Current Knowledge ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Tumor Evolution ◽  
Free Survival ◽  
Well Differentiated ◽  
Slow Growing ◽  
Therapeutic Responses

Well-differentiated neuroendocrine tumors (NETs) are a group of heterogeneous rare tumors. They are often slow-growing and patients can have very long survival, even at the metastatic stage. The evaluation of tumor progression and therapeutic responses is currently based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST) criteria. As for other malignancies, RECIST criteria are being reexamined for NETs in the era of targeted therapies because tumor response to targeted therapies is rarely associated with shrinkage, as opposed to prolonged progression-free survival. Therefore, size-based criteria no longer seem to be suitable to the assessment of NET progression and therapeutic responses, especially considering targeted therapies. New imaging criteria, combining morphological and functional techniques, have proven relevant for other malignancies treated with targeted therapies. To date, such studies have rarely been conducted on NETs. Moreover, optimizing the management of NET patients also requires considering clinical, biological, and pathological aspects of tumor evolution. Our objectives herein were to comprehensively review current knowledge on the assessment of tumor progression and early prediction of therapeutic responses and to broaden the outlook on well-differentiated NETs, in the era of targeted therapies.

Prognostic Value of the Human Kallikrein Gene 15 Expression in Ovarian Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3119-3126 ◽  
Author(s):  
George M. Yousef ◽  
Andreas Scorilas ◽  
Dionyssios Katsaros ◽  
Stefano Fracchioli ◽  
Lisa Iskander ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Benign Tumors ◽  
Rt Pcr ◽  
Free Survival ◽  
Kaplan Meier ◽  
Benign Ovarian Tumors

Purpose: KLK15 is a newly cloned human kallikrein gene. Many kallikreins were found to be differentially expressed in ovarian cancer. Like other kallikreins, KLK15 is regulated by steroid hormones in cancer cell lines. KLK15 is upregulated mainly by androgens and to a lesser extent by progestins. The purpose of this study was to examine the prognostic value of KLK15 in ovarian cancer tissues.Materials and Methods: We studied KLK15 expression by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 168 consecutive patients with epithelial ovarian cancer. Ten patients with benign ovarian tumors were also included in the study. An optimal cutoff point equal to the 50th percentile was defined based on the ability of KLK15 to predict progression-free survival and overall survival of the study population.Results: KLK15 expression levels were significantly higher in cancerous tissues compared with benign tumors. Kaplan-Meier survival curves showed that KLK15 overexpression is a significant predictor of reduced progression-free survival (PFS; P < .001) and overall survival (OS; P < .009). Univariate and multivariate analyses indicate that KLK15 is an independent prognostic factor for PFS and OS. A weak positive correlation was found between KLK15 expression and serum CA-125 levels.Conclusion: KLK15 expression, as assessed by quantitative RT-PCR, is an independent marker of unfavorable prognosis for ovarian cancer.

Classification of progression free survival with nasopharyngeal carcinoma tumors

2016 ◽  
Author(s):  
Hamidreza Farhidzadeh ◽  
Joo Y. Kim ◽  
Jacob G. Scott ◽  
Dmitry B. Goldgof ◽  
Lawrence O. Hall ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Progression Free Survival ◽  
Free Survival

Impact of consensus molecular subtyping (CMS) on overall survival (OS) and progression free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3511-3511 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Fang-Shu Ou ◽  
Alan P. Venook ◽  
Howard S. Hochster ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Proportional Hazard ◽  
First Line ◽  
Primary Tumors ◽  
Free Survival ◽  
First Line Therapy ◽  
Cox Proportional Hazard ◽  
Codon 12 And 13 ◽  
Clinical Trial Information

3511 Background: CALGB 80405 was a randomized Ph3 trial showing no OS or PFS difference in mCRC pts treated with Bevacizumab (BV) or Cetuximab (Cet) in the first line. A Nanostring platform was used to determine the CMS classification of 392 KRAS wt (codon 12 and 13) primary tumors and correlated it with OS and PFS in patients enrolled in 80405. Methods: CMS for 392 of 431tumors were defined using a custom CRC Nanostring panel (39 CMS classification not possible). Stratified Cox proportional hazard model was used to evaluate the effect of CMS classification stratified by prior radiation, prior chemotherapy, adjusting for age, sex, race, primary in place, liver met only, and sidedness. Results: We found CMS1 (14%), CMS2 (47%), CMS3 (2%), CMS4 (29%), NonConsensus (8%). Results are shown in Table 1. Patients with CMS1 who received BV had significantly longer OS than those who received Cet (HR 0.47, 95% CI [0.24, 0.92]). Patients with CMS2 who received BV tended to have shorter OS than those who received Cet (HR 1.41, CI [0.95, 2.08]). Conclusions: Our data suggest that CMS is associated with OS and PFS in first line therapy in mCRC patients. Preliminary data suggest that certain CMS may be associated with efficacy of Bev and Cet based chemotherapy. CMS classification should be explored as a stratification factor in future trials. Support: U10CA180821, U10CA180830, U10CA180882 Clinical trial information: NCT00265850. [Table: see text]

Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy

1994 ◽  
Vol 81 (5) ◽  
pp. 690-698 ◽  
Author(s):  
Roger J. Packer ◽  
Leslie N. Sutton ◽  
Roy Elterman ◽  
Beverly Lange ◽  
Joel Goldwein ◽  
...  
Keyword(s):  
Disease Control ◽  
Posterior Fossa ◽  
Metastatic Disease ◽  
Progression Free Survival ◽  
Age At Diagnosis ◽  
Entire Group ◽  
Subtotal Resection ◽  
Long Term Outcome ◽  
Free Survival ◽  
Reduced Dose

✓ It has previously been reported in a single-institution trial that progression-free survival of children with medulloblastoma treated with radiotherapy and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cisplatin, and vincristine chemotherapy during and after radiotherapy was better than the outcome in children treated with radiotherapy alone. To better characterize long-term outcome and duration of disease control, this treatment approach was used for 10 years and expanded to three institutions. Sixty-three children with posterior fossa medulloblastomas were treated with craniospinal local-boost radiotherapy and adjuvant chemotherapy with vincristine weekly during radiotherapy followed by eight 6-week cycles of cisplatin, CCNU, and vincristine. To be eligible for study entry, patients had to be older than 18 months of age at diagnosis and have a subtotal resection, evidence of metastatic disease, and/or brainstem involvement. Patients younger than 5 years of age and without these poor risk factors who received reduced-dose craniospinal radiotherapy (2400 cGy) were also eligible for entry into the study. Sixty-three of 66 eligible patients (95%) were entered and placed on this treatment regimen. Forty-two patients had brainstem involvement, 15 had metastatic disease at the time of diagnosis, and 19 had received a subtotal resection. Progression-free survival for the entire group at 5 years is 85% ± 6%. Three children have succumbed to a second malignancy, and overall 5-year event-free survival is 83% ± 6%. Progression-free survival was not adversely affected by younger age at diagnosis, brainstem involvement, or subtotal resection. Five-year actuarial progression-free survival for patients who received reduced-dose radiotherapy was similar to that for patients receiving conventional-dose radiotherapy. Patients with metastatic disease at the time of diagnosis had a 5-year progression-free survival rate of 67% ± 15%, as compared to 90% ± 6% for those patients with localized disease at the time of diagnosis (p = 0.037). The authors conclude that overall progression-free survival remains excellent for children with posterior fossa medulloblastomas treated with this drug regimen. Chemotherapy has a definite role in the management of children with medulloblastoma. Further studies are indicated to define which subpopulations of children with medulloblastoma benefit from chemotherapy and what regimens are optimum in increasing disease control and, possibly, in reducing the amount of radiotherapy required.

scholarly journals Targeted Sequencing Revealed Distinct Mutational Profiles of Ocular and Extraocular Sebaceous Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4810
Author(s):  
Hee Young Na ◽  
Jeong Hwan Park ◽  
Sun Ah Shin ◽  
Sejoon Lee ◽  
Heonyi Lee ◽  
...  
Keyword(s):  
Genetic Background ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Genetic Alterations ◽  
Sebaceous Carcinoma ◽  
Biological Behavior ◽  
Free Survival ◽  
Targeted Next Generation Sequencing ◽  
Repair Genes ◽  
Generation Sequencing

The biological behavior of sebaceous carcinoma (SeC) is relatively indolent; however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p < 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.

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