State-of-the-art considerations in small cell lung cancer brain metastases

Lukas, Rimas V.; Gondi, Vinai; Kamson, David Olayinka; Kumthekar, Priya; Salgia, Ravi

doi:10.18632/oncotarget.19333

Cited by 52 publications

(47 citation statements)

References 89 publications

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“…The brain is a common sanctuary site for SCLC metastases, and patients with CNS metastases typically have a poor prognosis [63]. The blood‐brain barrier limits the delivery of chemotherapy and ICIs to CNS disease, although T cells can more effectively cross, highlighting a potential role for ICIs in CNS metastases [64–66].…”

Section: Discussionmentioning

confidence: 99%

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

et al. 2020

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Background Small cell lung cancer (SCLC) represents approximately 15% of lung cancers, and approximately 70% are diagnosed as extensive‐stage SCLC (ES‐SCLC). Although ES‐SCLC is highly responsive to chemotherapy, patients typically progress rapidly, and there is an urgent need for new therapies. Immune checkpoint inhibitors (ICIs) have recently been investigated in SCLC, and this review provides guidance on the use of these agents in ES‐SCLC based on phase III evidence. Methods Published and presented literature on phase III data addressing use of ICIs in ES‐SCLC was identified using the key search terms “small cell lung cancer” AND “checkpoint inhibitors” (OR respective aliases). Directed searches of eligible studies were periodically performed to ensure capture of the most recent data. Results Six phase III trials were identified, with four assessing the benefits of ICIs plus chemotherapy first‐line, one evaluating ICIs as first‐line therapy maintenance, and one assessing ICI monotherapy after progression on platinum‐based chemotherapy. The addition of ipilimumab or tremelimumab to first‐line treatment or as first‐line maintenance did not improve survival. Two out of three studies combining PD‐1/PD‐L1 inhibitors with first‐line platinum‐based chemotherapy demonstrated significant long‐lasting survival benefits and improved quality of life with no unexpected safety concerns. PD‐1/PD‐L1 inhibitors as first‐line maintenance or in later lines of therapy did not improve survival. Biomarker research is ongoing as well as research into the role of ICIs in combination with radiation therapy in limited‐stage SCLC. Conclusion The addition of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy for ES‐SCLC prolongs survival and improves quality of life. Implications for Practice Platinum‐based chemotherapy has been standard of care for extensive‐stage small cell lung cancer (ES‐SCLC) for more than a decade. Six recent phase III trials investigating immune checkpoint inhibitors (ICIs) have clarified the role of these agents in this setting. Although ICIs were assessed first‐line, as first‐line maintenance, and in later lines of therapy, the additions of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy were the only interventions that significantly improved overall survival and increased quality of life. These combinations should therefore be considered standard therapy for first‐line ES‐SCLC. Biomarker research and investigations into the role of ICIs for limited‐stage disease are ongoing.

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Section: Discussionmentioning

confidence: 99%

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

et al. 2020

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“…There is also ample opportunity for the seed cells to find a receptive environment. [29]. It is possible that chemokines and adhesion molecules play an important role in lowering the risk of brain metastasis with larger tumor sizes and higher N stages [30].…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Different distant metastasis patterns based on tumor size could be found in extensive-stage small cell lung cancer patients: a large, population-based SEER study (v0.1)"

2019

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Small-cell lung cancer (SCLC) is a malignant cancer with the ability to metastasize quickly. The relationship between tumor size and the distant metastasis patterns of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) has not been reported. OBJECTIVES: The aim of this study was to determine the different distant metastasis patterns as they related to tumor size in ES-SCLC. PATIENTS AND METHODS: We used Surveillance, Epidemiology, and End Results (SEER) population-based data collected from 2010 through 2013 to identify 11058 ES-SCLC patients with definite evidence of distant metastases. Multivariate logistic regression analysis was used to demonstrate the association between tumor size and distant metastasis patterns including bone, liver, brain, and lung metastases. Age, race, sex, and N stage were also selected in the logistic regression model. RESULTS: Subtle differences in metastasis patterns were found among patients based on different tumor sizes. Patients with tumors 3-7 cm have a higher risk of bone metastasis compared with those that have tumors ≤ 3 cm (OR 1.165, 95% CI 1.055-1.287，P=0.003) and patients with tumors ≥7 cm have a higher risk of lung metastasis (OR 1.183, 95% CI 1.039-1.347，P=0.011). In addition, patients with tumors ≥7 cm had a lower risk of brain metastasis and liver metastasis than patients with tumors ≤ 3 cm(OR 0.799, 95% CI 0.709-0.901，P＜0.001;OR 0.747, 95% CI 0.672-0.830，P＜0.001). Interestingly, there was no correlation between a larger tumor and a higher risk of metastasis. However, the tumor metastasis pattern did have some correlation with age, gender, race and N-status. CONCLUSION: The pattern of distant metastasis of ES-SCLC is related to the tumor size and the tumor size is indicative of the metastatic site. Larger tumor sizes did not correlate with a higher risk of distant metastasis but the size is related

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“…Cells with different metastatic phenotypes first appear at the primary site, then cells with similar metastatic phenotypes cluster together and eventually metastasize to the different sites. Metastasis is a multi-step process in the cancer model, we think about mitogenesis, morphogenesis, and motogenesis [ 43 ]. The mitogenesis gives the proliferation that also then effects morpho- and moto-genesis.…”

Section: Sclc Metastasis and The Tumor Microenvironmentmentioning

confidence: 99%

Modeling small cell lung cancer (SCLC) biology through deterministic and stochastic mathematical models

et al. 2018

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Mathematical cancer models are immensely powerful tools that are based in part on the fractal nature of biological structures, such as the geometry of the lung. Cancers of the lung provide an opportune model to develop and apply algorithms that capture changes and disease phenotypes. We reviewed mathematical models that have been developed for biological sciences and applied them in the context of small cell lung cancer (SCLC) growth, mutational heterogeneity, and mechanisms of metastasis. The ultimate goal is to develop the stochastic and deterministic nature of this disease, to link this comprehensive set of tools back to its fractalness and to provide a platform for accurate biomarker development. These techniques may be particularly useful in the context of drug development research, such as combination with existing omics approaches. The integration of these tools will be important to further understand the biology of SCLC and ultimately develop novel therapeutics.

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State-of-the-art considerations in small cell lung cancer brain metastases

Cited by 52 publications

References 89 publications

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

Peer Review #2 of "Different distant metastasis patterns based on tumor size could be found in extensive-stage small cell lung cancer patients: a large, population-based SEER study (v0.1)"

Modeling small cell lung cancer (SCLC) biology through deterministic and stochastic mathematical models

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