Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling

Dean, Andrew; Byrne, Aisling; Marinova, Mira; Hayden, Ingrid

doi:10.1155/2016/4627214

Cited by 9 publications

(12 citation statements)

References 23 publications

(30 reference statements)

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“…Patients with rare tumors generally have limited treatment options (41). Utilizing TMB as a biomarker may help select such patients for immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers

Goodman

Kato

Bazhenova

et al. 2017

Molecular Cancer Therapeutics

1,898

1,554

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Immunotherapy induces durable responses in a subset of patients with cancer. High TMB may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non-small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. We reviewed data on 1,638 patients who had undergone comprehensive genomic profiling and had TMB assessment. Immunotherapy-treated patients (N = 151) were analyzed for response rate (RR), progression-free and overall survival (PFS, OS). Higher TMB was independently associated with better outcome parameters (multivariable analysis). The RR for patients with high (≥ 20 mutations/mb) vs. low to intermediate TMB was 22/38 (58%) vs. 23/113 (20%) (P = 0.0001); median PFS, 12.8 vs. 3.3 months (P = <0.0001); median OS, not reached vs. 16.3 months (P = 0.0036). Results were similar when anti-PD-1/PD-L1 monotherapy was analyzed (N = 102 patients), with a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders vs. non-responders treated with anti-PD-1/PD-L1 monotherapy was 18.0 vs. 5.0 mutations/mb (P < 0.0001). Interestingly, anti-CTLA4/anti-PD-1/PD-L1 combinations vs. anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%) (P = 0.004) and PFS (P = 0.024). Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. Benefit from dual checkpoint blockade did not show a similarly strong dependence on TMB.

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“…Patients with rare tumors generally have limited treatment options (41). Utilizing TMB as a biomarker may help select such patients for immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers

Goodman

Kato

Bazhenova

et al. 2017

Molecular Cancer Therapeutics

1,898

1,554

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“…Günümüzde kanser tedavisi seçimi, tümörlerin metastaz yaparken artan genetik heterojenitesine rağmen, tümörün moleküler özelliklerinden çok tümörün köken aldığı organa ve histolojik tipine dayanmaktadır. Ancak tümör biyolojisi konusundaki anlayışımız geliştikçe, tedaviye duyarlılığı öngörülen faktörlerin artan sayısı tespit edilebilecek ve tedaviyi yönlendirmek için hem yeni hedeflenmiş biyolojik ajanlar hem de kemoterapi protokolleri kullanılabilecektir (23) .…”

Section: Sonuçunclassified

Childhood Malign Solid Soft Tissue Sarcomas; Diagnostic, Histopathological and Molecular Approach

Yıldırım¹,

Yıldırım²,

Diniz³

et al. 2019

BUCH

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Childhood soft tissue sarcomas are heterogenous and be quite varied in apperance. Especially, these neoplasms known as "small round cell tumor" group, with their hyperchromatic nuclei and monotonous small and limited cytoplasm. These neoplasms share many similar histomorphological and immunophenotypic characteristics Also these lesions may often demonstrate similar clinical and radiological characteristics but have diverse prognoses. The purpose of this article is to review clinical, histologic, immunohistochemical features and molecular features of soft tissue sarcomas and discuss the differential diagnosis of these tumours.

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“…A minimal quantity of 100 mg that contains at least 50% of the target with excellent preservation is a requirement that has been generally accepted [15]. Macrobiopsies are recently available that can guarantee purity and quantity [16][17][18]. Dedicated fixators such as RNALater type of solutions can preserve the sample Fig.…”

Section: Sample Preparationmentioning

confidence: 99%

Preventive, predictive, and personalized medicine for effective and affordable cancer care

2018

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Preventive, predictive, and personalized medicine (PPPM) has created a wealth of new opportunities but added also new complexities and challenges. The European Cancer Prevention Organization already embraced unanimously molecular biology for primary and secondary prevention. The rapidly exploding genomic language and complexity of methods face oncologists with exponentially growing knowledge they need to assess and apply. Tissue specimen quality becomes one major concern. Some new innovative medicines cost beyond any reasonable threshold of financial support from patients, health care providers, and governments and risk sustainability for the health care system. In this review, we evaluate the path for genomic guidance to become the standard for diagnostics in cancer care and formulate potential solutions to simplify its implementation. Basically, introduction of molecular biology to guide therapeutic decisions can be facilitated through supporting the oncologist, the pathologist, the molecular laboratory, and the interventionist. Oncologists need to know the exact indication, utility, and limitations of each genomic service. Minimal requirements on the label must be addressed by the service provider. The interventionist is there to bring the most optimal tissue sample to pathology where the tissue is expanded to a variety of appropriate liquid-based samples. The large body of results then should be translated into meaningful clinical guidance for the individual patient. Surveillance, with the appropriate application of health economic indicators, can make this system long lasting. For governments and health care providers, optimal cancer care must result in a cost-effective, resource-sustainable, and patient-focused outcome.

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Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling

Cited by 9 publications

References 23 publications

Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers

Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers

Childhood Malign Solid Soft Tissue Sarcomas; Diagnostic, Histopathological and Molecular Approach

Preventive, predictive, and personalized medicine for effective and affordable cancer care

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