Study protocol: watchful observation of patients with limited small cell lung cancer instead of the PCI-prospective, multi-center one-arm study

Sergiusz Nawrocki, Anna Sugajska, Sergiusz Nawrocki, Anna Sugajska

Abstract

Background: Prophylactic cranial irradiation (PCI) is a current standard of care after confirmed response to radical chemoradiotherapy for limited disease small cell lung cancer (LD-SCLC). This standard is mostly based on results of old randomized studies when brain imaging with magnetic resonance (MRI) was not available. Survival benefit of PCI in extended disease SCLC was recently challenged by the results of randomized phase III study from Japan.

Methods: Eighty patients with LD-SCLC after response to chest chemoradiotherapy will be enrolled. Patients will be followed up by brain MRI every 3 to 6 months up to 3 years. Neurocognitive function tests will be performed at baseline and after 12 and 24 months. Patients who develop brain metastases will be irradiated with stereotactic (SRT) or whole brain RT (WBRT). The primary endpoint is overall survival. The secondary endpoints are: response rate to radiotherapy of early detected brain metastases, analysis of efficacy of SRT and WBRT; assessment and analysis of neurocognitive functions and QoL in the studied cohorts: QLQ-C30 questionnaire and the California Verbal Learning Test, Color connection test, Benton visual retention test, and verbal fluency test will be carried out.

Discussion: The results of this trial may contribute to changing of LD-SCLC clinical management by deescalating the treatment. There is a lack of prospective, recent studies in LD-SCLC patients with omission of PCI and modern radiation therapy technologies for developed brain metastases. The comprehensive neurocognitive function testing will help to assess the impact of modern radiotherapy (SRT) compared with WBRT and no-PCI in SCLC patients. A subgroup of long-term survivors, who will not develop brain metastases, will not be exposed to unnecessary brain irradiation with its deleterious consequences. The limitation of our study is a lack of parallel randomized control arm. This is a potential source of bias; however, randomized study will be difficult to complete for two major reasons: (1) limited population of LD-SCLC eligible for the study and (2) opinions of our patients, who after information and discussion about benefits and potential harms of PCI, often choose to omit PCI in our practice.

Trial registration: ClinicalTrials.gov Identifier: NCT04168281, 19 Nov. 2019.

Keywords: PCI; Prophylactic cranial irradiation; SRT; Small-cell lung cancer; Stereotactic radiotherapy.

Conflict of interest statement

The authors declare that they have no competing interests.

References

    1. Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic cranial irradiation overview collaborative group. N Engl J Med. 1999;341:476–484. doi: 10.1056/NEJM199908123410703.
    1. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357:664–672. doi: 10.1056/NEJMoa071780.
    1. Seute T, Leffers P, ten Velde GP, et al. Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI) Cancer. 2008;112:1837–1834. doi: 10.1002/cncr.23361.
    1. Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:663–667. doi: 10.1016/S1470-2045(17)30230-9.
    1. Lee YW, Cho HJ, Lee WH, Sonntag WE. Whole brain radiation-induced cognitive impairment: pathophysiological mechanisms and therapeutic targets. Biomol Ther (Seoul) 2012;20:357–370. doi: 10.4062/biomolther.2012.20.4.357.
    1. Ozawa Y, Omae M, Fujii M, et al. Management of brain metastasis with magnetic resonance imaging and stereotactic irradiation attenuated benefits of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer. BMC Cancer. 2015;15:589. doi: 10.1186/s12885-015-1593-2.
    1. Farooqi AS, et al. Prophylactic cranial irradiation after definitive chemoradiotherapy for limited-stage small cell lung cancer: do all patients benefit? Radiother Oncol. 2017;122(2):307–312. doi: 10.1016/j.radonc.2016.11.012.
    1. Slotman BJ, Mauer ME, Bottomley A, et al. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J Clin Oncol. 2009;27:78. doi: 10.1200/JCO.2008.17.0746.
    1. Johnson BE, Patronas N, Hayes W, et al. Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors. J Clin Oncol. 1990;8:48. doi: 10.1200/JCO.1990.8.1.48.
    1. Herskovic AM, Orton CG. Elective brain irradiation for small cell anaplastic lung cancer. Int J Radiat Oncol Biol Phys. 1986;12:427. doi: 10.1016/0360-3016(86)90363-9.
    1. Sheline GE, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys. 1980;6:1215. doi: 10.1016/0360-3016(80)90175-3.
    1. Arriagada R, Le Chevalier T, Borie F, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst. 1995;87:183. doi: 10.1093/jnci/87.3.183.
    1. Gregor A, Cull A, Stephens RJ, et al. Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC) Eur J Cancer. 1997;33:1752. doi: 10.1016/S0959-8049(97)00135-4.
    1. Wolfson AH, Bae K, Komaki R, et al. Primary analysis of a phase II randomized trial radiation therapy oncology group (RTOG) 0212: impact of different total doses and schedules of prophylactic cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;81:77. doi: 10.1016/j.ijrobp.2010.05.013.
    1. Wolfson AH, Bains Y, Lu J, et al. Twice-daily prophylactic cranial irradiation for patients with limited disease small-cell lung cancer with complete response to chemotherapy and consolidative radiotherapy: report of a single institutional phase II trial. Am J Clin Oncol. 2001;24:290. doi: 10.1097/00000421-200106000-00017.
    1. Khuntia D, Brown P, Li J, Mehta MP. Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol. 2006;24:1295. doi: 10.1200/JCO.2005.04.6185.
    1. Osowiecka K, Rucińska M, Suszko-Każarnowicz M, Nawrocki S. Przeżycia chorych na drobnokomórkowego raka płuca leczonych napromienianiem w latach 2003–2006 w Samodzielnym Publicznym Zakładzie Opieki Zdrowotnej Ministerstwa Spraw Wewnętrznych z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie. Nowotwory J Oncol. 2013;63(5):395–402. doi: 10.5603/NJO.2013.0036.

Source: PubMed

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