Survival curve

Another member of the FGF family, FGF-4, protects against radiation-iaduced ceU killing and enhanced the G2 arrest when overexpressed ia a human adrenal cortical carcinoma ceU line (196). This effect is again manifested as the appearance of a shoulder on the survival curve, although neither the control nor the transfected cells undergo radiation-iaduced apoptosis. No differences ia the yield or repair of either SSBs or DSBs have been observed. 

Barendsen, G.W. 1990. Mechanisms of cell reproductive death and shapes of radiation dose-survival curves of mammalian cells. Inter. Jour. Radiation Biol. 57 885-896. 

Figure 39. Survival Curves Predicted for 70-kg Man Applicable to Free-Stream Situations Where the Long Axis of the Body is Perpendicular to the Direction of Propagation of the Shocked Blast Wave. (Ref. 43)...

Breslow, N. (1984). Comparison of survival curves. In Cancer Clinical Trials Methods and Practice (Buyse, M.E., Staquet, M.J. and Sylvester, R.J., Eds.). Oxford University Press, Oxford, pp. 381 106. 

Evaluation of the data surrounding the death by physicians who are unassociated with the clinical trial lends additional credibility to the report and conclusions. Physician biases probably will strongly influence their decision regarding the association of a patient s death with the clinical trial, and this factor must be considered in interpreting their report. This is particularly true for developing survival curves in cancer or other often fatal diseases, when deaths unrelated to the disease or to the treatment are excluded from the analysis. 

Fig. 4.8 Survival curves of (A) LLC, J774, CT26 cells after 24 h incubation with 2 iM BF4 and (B) J774 cells after 24h incubation with 2 lM BF1—BF6, in both cases followed by a wash and illumination with white light. An MTT assay was carried out after 24 h incubation. Values are means of nine separate wells and bars are SD. Experiments were repeated at least twice...

A statistical technique used to test the significance of differences between the survival curves associated with two different treatments. It is often used to analyze survival (life vs. death) data when there are censored observations (observations that are unknown because a subject has not been in the study long enough for the outcome to be observed) or to analyze the effects of different treatment procedures. ... 

Figure 2 Effect of liposomal formulations BPs (alendronate and clodronate), empty and free drugs on RAW 264 cell survival. Curves represent percentage of cell inhibition with different BP concentrations. Cell count in buffer only was determined to be 100% (n = 3). Abbreviation BPs, bisphosphonates. Source From Ref 69.

Fig. 8. Diagram of 5-FU radiosensitization. Curve 1 Radiation survival curve for cells not treated with 5-FU. Curve 2 Radiation survival curve for cells treated postradiation with sufficient 5-FU to kill 50% of the cells without radiation (partial response equivalent). Curve 3 Radiation survival curve with 5-FU killing to 10% (typical of cell system very sensitive to 5-FU).

In vitro studies have shown that paclitaxel is a potent radiation sensitizer. Survival curves using grade 3 human astrocytoma cell lines showed a sensitizer enhancement ratio of 1.8 (57). In a series of experiments using a human leukemic cell line (HL-60), a sensitizing enhancement ratio of 1.48 was noted (58). Other studies have shown that G2/M block is not the only mechanism of paclitaxel-induced radiosensitization (59). 

Percentages were estimated from survival curves. 

Fig. 6. (A) Western blot analysis of COX-2 levels in RIE-S and RIE-AS cells. +ve, COX-2 protein positive control. Survival curves for radiation plus NS-398 in RIE-S (B) and RIE-AS (C) cells. (O), radiation plus vehicle (DMSO) treatment ( ), radiation plus 150 pM NS-398 treatment ( ), radiation plus 300 pM NS-398 treatment (A), radiation plus 400 pM NS-398 treatment.

Survival curves in MADIT II did not separate until 9 months after enrollment, raising the question of when an ICD should be implanted after MI or revascularization. Two notable negative primary prevention trials may answer this question. The Coronary Artery Bypass Graft Patch (CABG-Patch) Trial evaluated whether primary prevention with ICD at the time of surgical revascularization in patients with EF < 35% and a positive SAECG would reduce total mortality [33]. At 32 months follow-up, no difference was found, suggesting that there is no additional benefit to ICD therapy at the time of revascularization. 

Fig. 6. Survival curves of ATL groups classified according to mFas (A) and sFas status (B). Prognosis could not be predicted by mFas status (a v. b), but could be predicted by sFas status (c v. d), suggesting that the sFas isoform plays a more important role in tumor biology than mFas in some ATL cases.

Throughout this section we will adopt the conventions of the area and refer to survival analysis and survival curves, accepting that the methods are applied more widely to events other then death. 

Kaplan and Meier (1958) introduced a methodology for estimating, from censored survival data, the probability of being event-free as a function of time. If the event is death then we are estimating the probability of surviving and the resultant plots of the estimated probability of surviving as a function of time are called either Kaplan-Meier (KM) curves or survival curves. 

A placebo-controlled randomised trial reported by Packer et al. (2001) investigated the effect of carvedilol on survival time in severe heart failure. Figure 13.1 shows the survival curve for each of the two treatment groups following the early termination of the trial at a planned interim analysis. 

Figure 13.1 Kaplan-Meier survival curves in placebo and carvedilol groups (Packer M, Coats AJS, Fowler MB, et al. for the Carvedilol Prospective Randomised Cumulative Survival Study Group, Effect of carvedilol on survival in severe chronic heart failure. New England Journal of Medicine, 344, 1651-1658. (2001) Massachusetts Medical Society.)...

The Kaplan-Meier curves do not of themselves provide a formal, p-value, comparison of the treatments. This comparison of the survival curves is undertaken using either the logrank test or the Gehan-Wilcoxon test. We will look at these two test procedures in turn. 

Figure 13.2 provides two sets of hypothetical population survival curves. In part a) the curves are seen to separate out gradually over the period of follow-up. In contrast, the curves in part b) separate out fairly rapidly, but then start to converge later on in time. 

In an earlier section we saw two different patterns for two sets of survival curves. In Figure 13.2 a) the survival curves move further and further apart as time moves on. This pattern is consistent with one of the hazard rates (think in terms of death rates) being consistently above the other hazard rate. This in turn corresponds to a fairly constant hazard ratio, the situation we discussed in Section 13.4.1. So a constant hazard ratio manifests itself as a continuing separation in the two survival curves as in Figure 13.2 a). Note that the higher hazard rate (more deaths) gives the lower of the two survival curves. 

Figure 7 Survival curves of human kidney cells T1 irradiated under hypoxic and aerobic conditions with different qualities of radiation (a) 250-kV x-rays (LET of about 1.3 keV (b) 14-MeV...

In order to compare mutation frequency induced by 220-MeV C ions with that by low-LET radiation (electrons), Arabidopsis visible phenotype loci were chosen as follows transparent testa tt) whose seed coat is transparent because of lack of pigment glaborous gl), which have no hair on their leaves and stems and long hypocotyl hy) whose hypocotyl is longer than that of the wild type in the light condition. Mutation frequencies of tt, gl, and hy induced by carbon ions were 8- to 34-fold higher than those by electrons (Table 2). In this study, irradiation doses for the induction of mutation were determined from the RBE of carbon ions compared with that of electrons on the survival of plants, which was approximately 5. Both doses are at three-quarters of the shoulder dose of each survival curve [104]. 

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