scholarly journals How mathematical modeling could contribute to the quantification of metastatic tumor burden under therapy: insights in immunotherapeutic treatment of non-small cell lung cancer

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Pirmin Schlicke ◽  
Christina Kuttler ◽  
Christian Schumann
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Diagnosis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Prognostic Features ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy

Abstract Background Cancer is one of the leading death causes globally with about 8.2 million deaths per year and an increase in numbers in recent years. About 90% of cancer deaths do not occur due to primary tumors but due to metastases, of which most are not clinically identifiable because of their relatively small size at primary diagnosis and limited technical possibilities. However, therapeutic decisions are formed depending on the existence of metastases and their properties. Therefore non-identified metastases might have huge influence in the treatment outcome. The quantification of clinically visible and invisible metastases is important for the choice of an optimal treatment of the individual patient as it could clarify the burden of non-identifiable tumors as well as the future behavior of the cancerous disease. Results The mathematical model presented in this study gives insights in how this could be achieved, taking into account different treatment possibilities and therefore being able to compare therapy schedules for individual patients with different clinical parameters. The framework was tested on three patients with non-small cell lung cancer, one of the deadliest types of cancer worldwide, and clinical history including platinum-based chemotherapy and PD-L1-targeted immunotherapy. Results yield promising insights into the framework to establish methods to quantify effects of different therapy methods and prognostic features for individual patients already at stage of primary diagnosis.

scholarly journals How Mathematical Modeling Could Contribute to the Quantification of Metastatic Tumor Burden Under Therapy: Insights in Immunotherapeutic Treatment of Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Pirmin Schlicke ◽  
Christina Kuttler ◽  
Christian Schumann
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Diagnosis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Prognostic Features ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy

Abstract Background: Cancer is one of the leading death causes globally with about 8.2 million deaths per year and an increase in numbers in recent years. About 90% of cancer deaths do not occur due to primary tumors but due to metastases, of which most are not clinically identifiable because of their relatively small size at primary diagnosis and limited technical possibilities. However, therapeutic decisions are formed depending on the existence of metastases and their properties. Therefore non-identified metastases might have huge influence in the treatment outcome. The quantification of clinically visible and invisible metastases is important for the choice of an optimal treatment of the individual patient as it could clarify the burden of non identifiable tumors as well as the future behavior of the cancerous disease. Results: The mathematical model presented in this study gives insights in how this could be achieved, taking into account different treatment possibilities and therefore being able to compare therapy schedules for individual patients with different clinical parameters. The framework was tested on three patients with non-small cell lung cancer, one of the deadliest types of cancer worldwide, and clinical history including platinum-based chemotherapy and PD-L1-targeted immunotherapy. Results yield promising insights into the framework to establish methods to quantify effects of different therapy methods and prognostic features for individual patients already at stage of primary diagnosis.

scholarly journals A Patient with an Ileocecal MiNEN and a Synchronous Squamous Non-Small-Cell Lung Cancer: Case Report and Review of the Literature

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Santiago Teran ◽  
Maria Camara Jurado ◽  
Juan Antonio Nuñez Sobrino
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cancer Case ◽  
Neuroendocrine Neoplasms ◽  
Platinum Resistance ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Platinum Based Chemotherapy

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare tumors composed of two different histological components, one of which is of a neuroendocrine origin. Given its suggested underdiagnosis and consequent low prevalence, no clear diagnostic and treatment guidelines are available, and treatment usually follows regimens similar to that of the most aggressive component. On the other hand, multiple primary tumors (MPTs) are also rare neoplastic entities that usually confer a challenge regarding treatment options, for a regimen that comprises both the primary and the synchronous/metachronous malignancy should be used. Here, we discuss the challenging diagnostic and therapeutic management of a patient with an ileocecal MiNEN that presented along with a synchronous squamous non-small-cell lung cancer (SQ-NSCLC). The patient presented with intestinal obstruction symptoms for which he underwent an emergency resection of the ileocecal MiNEN. An initial CT scan showed an additional lung mass later identified as an SQ-NSCLC after bronchoscopy biopsy analysis. Given the rapid hepatic metastatic progression, palliative platinum-based chemotherapy was initiated, with an adequate response of the local and metastatic lesions of the MiNEN, but suggested platinum resistance and progression of the pulmonary neoplasm. Second-line treatment with pembrolizumab directed for the SQ-NSCLC was initiated; however, it was stopped after immune-mediated toxicities developed. A third-line chemotherapy scheme with carboplatin/gemcitabine was initiated, but central nervous system (CNS) progression developed, with the patient dying 11 months after initial diagnosis.

scholarly journals Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Katrina Kildey ◽  
Neha S. Gandhi ◽  
Katherine B. Sahin ◽  
Esha T. Shah ◽  
Eric Boittier ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genome Instability ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Levels ◽  
Platinum Based Chemotherapy ◽  
Platinum Agents

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.

scholarly journals Polymorphisms in the Gene Encoding Caspase 8 May Predict the Response to First-Line Platinum-Based Chemotherapy in Locally Advanced or Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 10 (5) ◽  
pp. 1126
Author(s):  
Michał Szczyrek ◽  
Radosław Mlak ◽  
Aneta Szudy-Szczyrek ◽  
Karolina Kędziora ◽  
Teresa Małecka-Massalska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Small Cell ◽  
Caspase 8 ◽  
Small Cell Lung ◽  
Gene Encoding ◽  
Platinum Based Chemotherapy

Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS).

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