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    Gamma-Knife success depends on time of day?

    Gamma knife radiosurgery for brain metastasis of nonsmall cell lung cancer: is there a difference in outcome between morning and afternoon treatment?

    Rahn DA 3rd, Ray DK, Schlesinger DJ, Steiner L, Sheehan JP, O'Quigley JM, Rich T.

    Department of Radiation Oncology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.

    Abstract

    BACKGROUND:

    Circadian cell-cycle progression causes fluctuating radiosensitivity in many tissues, which could affect clinical outcomes. The purpose of this study was to determine whether outcomes of single-session gamma knife radiosurgery (GKRS) for metastatic nonsmall cell lung cancer (NSCLC) differ based on treatment time.

    METHODS:

    Fifty-eight patients received GKRS between 10:00 am and 12:30 pm and 39 patients received GKRS between 12:30 pm and 3:00 pm. The mean peripheral dose was 18.6 Gy. The mean tumor size was 7.3 cm³. Magnetic resonance imaging was used to score local control at 3 months. Cause of death (COD) was categorized as central nervous system (CNS)-related or systemic.

    RESULTS:

    Demographic and disease characteristics of the 2 groups were similar. Local control at 3 months was achieved in 97% (35/36) of patients who underwent GKRS early in the day versus 67% (8/12) of patients who underwent GKRS later in the day (chi-square, P = .014). Early GKRS was associated with better survival (median 9.5 months) than late GKRS (median 5 months) (Kaplan-Meier log-rank test, P = .025). Factors contributing to better survival in a Cox regression model included early treatment time (P = .004) and recursive partition analysis class (P < .001). Cause of death in the early treatment group was CNS-related in 6% (3/47) of patients versus 24% (8/34) of patients in the late treatment group (chi-square test, P = .026).

    CONCLUSIONS:

    GKRS for metastatic NSCLC had better local control, better survival, and a lower rate of CNS-related cause of death when given earlier in the day versus later in the day. These retrospective data should encourage future study in brain radiosurgery and non-CNS stereotactic body radiotherapy series.

    Source: Cancer. 2011 Jan 15;117(2):414-20. doi: 10.1002/cncr.25423. Epub 2010 Sep 9.
    Gregory D. Pawelski

    #2
    Circadian Physiology

    The earlier in the day concept has some basis in cancer biology. Apparently, this "circadian" issue is talked alot in medical oncology. This is the first heard of it in radiation oncology.

    Circadian physiology highlights the basic processes and latest research findings in circadian biology and describes how this knowledge applies to the timing for effective administration of medicines. The formal study of biological temporal rhythms is called chronobiology.

    According to Wiki, photosensitive proteins and circadian rhythms are believed to have originated in the earliest cells, with the purpose of protecting the replicating of DNA from high ultraviolet radiation during the daytime. As a result, replication was relegated to the dark.

    Circadian rhythms allow organisms to anticipate and prepare for precise and regular environmental changes; they have great value in relation to the outside world. The rhythmicity appears to be as important in regulating and coordinating internal metabolic processes, as in coordinating with the environment.

    Many more genetic components of the biological clock are now known. Their interactions result in an interlocked feedback loop of gene products resulting in periodic fluctuations that the cells of the body interpret as a specific time of the day.
    Gregory D. Pawelski

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