A SNaPshot of potentially personalized care: Molecular diagnostics in gynecologic cancer

Penson, Richard T.; Sales, Elizabeth; Sullivan, Laura A.; Borger, Darrell R.; Krasner, Carolyn; Goodman, Annekathryn; Carmen, M.G. del; Growdon, Whitfield B.; Schorge, John O.; Boruta, David M.; Castro, Cesar M.; Dizon, Don S.; Birrer, Michael J.

doi:10.1016/j.ygyno.2016.02.032

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…During the study timeframe, genotyping was quickly replaced by broader next-generation sequencing of 500-1000 full gene sequencing. 19 In the majority of our gynecologic cancer cases, molecular analysis identified an actionable target; however, only in a third of these cases was the course of treatment changed which is comparable to current literature in other disease sites. 20 Our study identified that changes in treatment occurred most frequently in patients with endometrial/uterine cancers, followed by ovarian cancer compared to patients with cervical and vulvar cancer where few changes were made.…”

Section: Discussionsupporting

confidence: 79%

“…During the study timeframe, genotyping was quickly replaced by broader next-generation sequencing of 500-1000 full gene sequencing. 19 In the majority of our gynecologic cancer cases, molecular analysis identified an 20 Our study identified that changes in treatment occurred most frequently in patients with endometrial/uterine cancers, followed by ovarian cancer compared to patients with cervical and vulvar cancer where few changes were made. In a recent study of 149 vulvar cancer cases, a variety of mutations were identified, with the following occurring most commonly: TP53 (33%), BRCA 2 (10%), HRAS (5%), FBXW7 (4%), and PIK3CA (3%).…”

Section: Discussionmentioning

confidence: 75%

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Impact of molecular testing in clinical practice in gynecologic cancers

et al. 2019

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Background With the growing understanding of the molecular and genetic profiles of cancers, targeted treatments are increasingly utilized in personalized cancer care. The objective of this study was to determine how these advances have translated into practice by examining how often molecular profiling of gynecological tumors led to treatment changes. Methods We identified women with gynecological cancers at our institution who had molecular tumor testing performed from November 2014 to June 2017. Clinicopathologic data were extracted from medical records. We determined (a) if molecular profiling identified actionable targets for which therapy is available, and (b) whether the patient's treatment course changed as a result of molecular profiling. Chi‐square, Wilcoxon rank‐sum, and Fisher's exact tests were used with a P < 0.05 considered statistically significant. Results We identified 152 patients with gynecologic cancers who underwent molecular profiling. Of the 152 patients, 116 (76.3%) had actionable mutations identified, with 41 (35.3%) patients having a treatment change. Stratified by cancer type, molecular profiling most frequently identified an actionable target in patients with endometrial cancer (73.6%). Changes in treatment occurred most frequently in patients with endometrial cancer, 22 (56.4%), and ovarian cancers, 16 (39%), as compared to patients with cervical and vulvar cancer ( P = 0.02). Of those patients who received a change in treatment, 39 patients (95.1%) received an FDA‐approved therapeutic agent, while two patients (4.8%) were enrolled in a clinical trial. Conclusion Molecular profiling in gynecologic cancers often identified at least one actionable mutation; however, only in a minority of these cases was the course of treatment changed. Further studies are needed to elucidate optimal timing for testing to best utilize actionable information.

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Section: Discussionsupporting

confidence: 79%

“…During the study timeframe, genotyping was quickly replaced by broader next-generation sequencing of 500-1000 full gene sequencing. 19 In the majority of our gynecologic cancer cases, molecular analysis identified an 20 Our study identified that changes in treatment occurred most frequently in patients with endometrial/uterine cancers, followed by ovarian cancer compared to patients with cervical and vulvar cancer where few changes were made. In a recent study of 149 vulvar cancer cases, a variety of mutations were identified, with the following occurring most commonly: TP53 (33%), BRCA 2 (10%), HRAS (5%), FBXW7 (4%), and PIK3CA (3%).…”

Section: Discussionmentioning

confidence: 75%

Impact of molecular testing in clinical practice in gynecologic cancers

et al. 2019

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“…Six studies (8%) gathering 1,106 participants informed the presence of this mutation [24,27,29,46,48,57]. A quantitative synthesis of all studies was not performed since two different groups were clearly identified; four studies with 970 participants informed very low positivity rates (globally 2%; 95%CI: 0%-5%) and two studies including 136 participants reported high positivity rates (total 88%; 95%CI: 82%-93%) ( Figure 11, Appendix D).…”

Section: Aktmentioning

confidence: 99%

“…Raf mutations were informed in six studies (8%) with a total of 349 participants [6,15,27,37,42,79]. The pooled estimate for positivity rate was 1% (95%CI: 0%-4%; I 2 = 38%; Figure 12, Appendix D).…”

Section: Rafmentioning

confidence: 99%

A systematic review and meta-analysis of the prevalence of therapeutic targets in cervical cancer

Patrono

Calvo

Franco

et al. 2021

ecancer

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Cervical Cancer (CC) is a significantly prevalent disease in developing countries. Currently, targeted therapies are not a primary standard of care in CC. This information could be crucial for developing directed therapies and patient screening for biomarkers that would allow personalised treatment of CC. This systematic review aimed to estimate the prevalence of potential therapeutic targets such as the epidermal growth factor receptor (EGFR) and the PI3K/Akt/mTOR and Ras/Raf/MAPK pathways in patients with CC, identified through genomic and non-genomic testing. Studies were identified through an ad-hoc search strategy from the available on MEDLINE (Ovid), CENTRAL, LILACS, SCOPUS, through the Clinical Trial registry on Clinicaltrials.gov, International Clinical Trials Registry Platform, RENIS (Argentine National Registry of Health Research) and grey literature sources. We included 74 studies which represented a total pool of 7,862 participants. Forty-five studies informed mutations of EGFR, with a combined positivity rate of 53% (95%CI: 45%-60%; I 2 = 95%). Twenty studies informed the presence of mutations in PIK3CA with a combined positivity rate of 30% (95%CI: 21%-39%; I 2 = 96%). Twentythree studies reported a mutation in Ras, with a combined positivity rate of 14% (95%CI: 8%-21%; I 2 = 95%). Raf mutations were informed in six studies. Six studies informed the presence of Akt mutations, two studies informed mTOR mutations and only one study reported mutations of MAPK. The most frequently described therapeutic targets were EGFR, and the PIK3CA and Ras pathways, though inconsistency in positivity rates was significant. Our study did not allow the identification of any specific clinical characteristics that might explain the observed heterogeneity. Despite the overall good quality of the included studies, the applicability of these results to patients' general population with CC is still unclear.

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“…Conventionally, tumor tissue biopsy is used for histological and molecular analysis, including fusion identification [11]. In the context of CNS tumors, this procedure is highly invasive and serial biopsies are not practical to capture temporal and spatial tumor heterogeneity [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma

Wang

Yekula

Muralidharan

et al. 2020

Cancers

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Sequencing studies have provided novel insights into the heterogeneous molecular landscape of glioblastoma (GBM), unveiling a subset of patients with gene fusions. Tissue biopsy is highly invasive, limited by sampling frequency and incompletely representative of intra-tumor heterogeneity. Extracellular vesicle-based liquid biopsy provides a minimally invasive alternative to diagnose and monitor tumor-specific molecular aberrations in patient biofluids. Here, we used targeted RNA sequencing to screen GBM tissue and the matched plasma of patients (n = 9) for RNA fusion transcripts. We identified two novel fusion transcripts in GBM tissue and five novel fusions in the matched plasma of GBM patients. The fusion transcripts FGFR3-TACC3 and VTI1A-TCF7L2 were detected in both tissue and matched plasma. A longitudinal follow-up of a GBM patient with a FGFR3-TACC3 positive glioma revealed the potential of monitoring RNA fusions in plasma. In summary, we report a sensitive RNA-seq-based liquid biopsy strategy to detect RNA level fusion status in the plasma of GBM patients.

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A SNaPshot of potentially personalized care: Molecular diagnostics in gynecologic cancer

Cited by 6 publications

References 19 publications

Impact of molecular testing in clinical practice in gynecologic cancers

Impact of molecular testing in clinical practice in gynecologic cancers

A systematic review and meta-analysis of the prevalence of therapeutic targets in cervical cancer

Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma

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