Factors influencing the utilization of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer

Lok, Benjamin H.; Ma, Jennifer; Foster, Amanda; Perez, C.A.; Shi, Wei; Zhang, Zhigang; Li, Bob T.; Rudin, Charles M.; Rimner, Andreas; Wu, Abraham J.

doi:10.1016/j.adro.2017.08.001

Cited by 43 publications

(36 citation statements)

References 23 publications

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“…In a more recent Japanese phase III trial 36 , in which pretreatment brain imaging was mandated, PCI did not improve the overall survival of patients with ES-SCLC. Of note, both patients and physicians have concerns regarding the potential for delayed PCI-related neurotoxicity, which must be balanced with the need to achieve disease control 37,38 .…”

Section: Clinical Overviewmentioning

confidence: 99%

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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Section: Clinical Overviewmentioning

confidence: 99%

Unravelling the biology of SCLC: implications for therapy

et al. 2017

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“…The PCI regimens used in the trials were heterogeneous, ranging from 8 Gy/1 fraction to 40 Gy/20 fractions (40). Although this meta-analysis demonstrated the efficacy of PCI in reducing BM and improving OS (41,42), reasons to withhold PCI include its negative impact on neurocognition and quality of life (QoL) (43,44). In an RCT of 720 LS-SCLC with CR following CRT, standard-dose PCI (25 Gy/10 fractions) was compared to high-dose PCI (36 Gy/18 fractions), with the standard dose demonstrating improved 2year OS (42 vs. 37%, p = 0.05).…”

Section: Prophylactic Cranial Irradiation In Ls-sclcmentioning

confidence: 99%

Current Management and Progress in Radiotherapy for Small Cell Lung Cancer

et al. 2020

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Radiotherapy (RT) and chemotherapy continue to be widely utilized in small cell lung cancer (SCLC) management. In most limited stage (LS)-SCLC cases, the standard initial therapy remains concurrent chemoradiotherapy (CRT), typically with an etoposide and platinum-based regimen. Hyperfractionated twice daily (BID) RT remains the standard of care, though conventional daily (QD) RT is now a viable alternative supported by randomized evidence. In LS-SCLC patients who experienced good response to CRT, prophylactic cranial irradiation (PCI) remains the standard of care. Brain imaging, ideally with MRI, should be performed prior to PCI to screen for clinically apparent brain metastases that may require a higher dose of cranial irradiation. Platinum doublet chemotherapy alone is the historic standard initial therapy in extensive stage (ES)-SCLC. Addition of immunotherapy such as atezolizumab and durvalumab to chemotherapy is now recommended after their benefits were demonstrated in recent trials. In patients with response to chemotherapy, consolidation thoracic RT and PCI could be considered, though with caveats. Emergence of hippocampal avoidance cranial irradiation and SRS in SCLC patients may supplant whole cranial irradiation as future standards of care. Incorporation of novel systemic therapies such as immunotherapies has changed the treatment paradigm and overall outlook of patients with SCLC. This narrative review summarizes the current state, ongoing trials, and future directions of radiotherapy in management of SCLC.

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“…Indeed, approximately 40% of patients with LS-SCLC do not receive PCI, primarily because of concerns over toxicity. 55,56 A pooled analysis of the Radiation Therapy Oncology Group (RTOG) 0212 and 0214 trials 57 reported inferior performance on cognitive testing and a more than threefold increase in patient-reported cognitive dysfunction with PCI at both 6 and 12 months (Fig. 2).…”

Section: Qol Cognition and The Risk-benefit Assessmentmentioning

confidence: 99%

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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Factors influencing the utilization of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer

Cited by 43 publications

References 23 publications

Unravelling the biology of SCLC: implications for therapy

Unravelling the biology of SCLC: implications for therapy

Current Management and Progress in Radiotherapy for Small Cell Lung Cancer

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

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