The Factors Influencing the Utilization of Prophylactic Cranial Irradiation in Patients With Limited-Stage Small Cell Lung Cancer

Lok, Benjamin H.; Pietanza, M. Catherine; Foster, Amanda; Rudin, Charles M.; Perez, C.A.; Ong, Leonard; Krug, Lee M.; Rimner, Andreas; Wu, Abraham J.

doi:10.1016/j.ijrobp.2015.07.1619

Cited by 3 publications

(1 citation statement)

References 17 publications

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“…These trials have consistently shown that PCI leads to a reduction in the incidence of brain metastases and a prolongation in survival in patients with limited disease with initial response [ 65 , 66 ]. In spite of the compelling evidence supporting the use of PCI, a recent study demonstrated that 40% of SCLC patients for whom a survival benefit from PCI has been shown, do not receive PCI due to concerns of cognitive toxicity on the part of both patient and physician [ 67 ]. A recent trial of PCI for limited-stage SCLC demonstrated a 62% (95% confidence interval 50–74%) rate of cognitive toxicity [ 68 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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BackgroundSmall cell lung cancer (SCLC) frequently leads to development of brain metastases. These unfortunately continue to be associated with short survival. Substantial advances have been made in our understanding of the underlying biology of disease. This understanding on the background of previously evaluated and currently utilized therapeutic treatments can help guide the next steps in investigations into this disease with the potential to influence future treatments.DesignA comprehensive review of the literature covering epidemiology, pathophysiology, imaging characteristics, prognosis, and therapeutic management of SCLC brain metastases was performed.ResultsSCLC brain metastases continue to have a poor prognosis. Both unique aspects of SCLC brain metastases as well as features seen more universally across other solid tumor brain metastases are discussed. Systemic therapeutic studies and radiotherapeutic approaches are reviewed.ConclusionsA clearer understanding of SCLC brain metastases will help lay the framework for studies which will hopefully translate into meaningful therapeutic options for these patients.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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Prophylactic Cranial Irradiation (PCI) versus Active MRI Surveillance for Small Cell Lung Cancer: The Case for Equipoise

Rusthoven

Kavanagh

2017

Journal of Thoracic Oncology

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Prophylactic cranial irradiation (PCI) for SCLC offers a consistent reduction in the incidence of brain metastases at the cost of measurable toxicity to neurocognitive function and quality of life, in the setting of characteristic pathologic changes to the brain. The sequelae of PCI have historically been justified by the perception of an overall survival advantage specific to SCLC. This rationale has now been challenged by a randomized trial in extensive-stage SCLC demonstrating equivalent progression-free survival and a trend toward improved overall survival with PCI omission in the context of modern magnetic resonance imaging (MRI) staging and surveillance. In this article, we critically examine the randomized trials of PCI in extensive-stage SCLC and discuss their implications on the historical data supporting PCI for limited-stage SCLC from the pre-MRI era. Further, we review the toxicity of moderate doses of radiation to the entire brain that underlie the growing interest in active MRI surveillance and PCI omission. Finally, the evidence supporting prospective investigation of radiosurgery for limited brain metastases in SCLC is reviewed. Overall, our aim is to provide an evidence-based assessment of the debate over PCI versus active MRI surveillance and to highlight the need for contemporary trials evaluating optimal central nervous system management in SCLC.

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Unravelling the biology of SCLC: implications for therapy

et al. 2017

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Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are being clinically tested in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints. Preclinical data indicate that targeting of histone-lysine N-methyltransferase EZH2, a regulator of chromatin remodelling implicated in acquired therapeutic resistance, might augment and prolong chemotherapy responses. High expression of the inhibitory Notch ligand Delta-like protein 3 (DLL3) in most SCLCs has been linked to expression of Achaetescute homologue 1 (ASCL1; also known as ASH-1), a key transcription factor driving SCLC oncogenesis; encouraging preclinical and clinical activity has been demonstrated for an anti-DLL3-antibody–drug conjugate. The immune microenvironment of SCLC seems to be distinct from that of other solid tumours, with few tumour-infiltrating lymphocytes and low levels of the immune-checkpoint protein programmed cell death 1 ligand 1 (PD-L1). Nonetheless, immunotherapy with immune-checkpoint inhibitors holds promise for patients with this disease, independent of PD-L1 status. Herein, we review the progress made in uncovering aspects of the biology of SCLC and its microenvironment that are defining new therapeutic strategies and offering renewed hope for patients.

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The Factors Influencing the Utilization of Prophylactic Cranial Irradiation in Patients With Limited-Stage Small Cell Lung Cancer

Cited by 3 publications

References 17 publications

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

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

Prophylactic Cranial Irradiation (PCI) versus Active MRI Surveillance for Small Cell Lung Cancer: The Case for Equipoise

Unravelling the biology of SCLC: implications for therapy

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