Effect of Changes in MS Diagnostic Criteria Over 25 Years on Time to Treatment and Prognosis in Patients With Clinically Isolated Syndrome

Objectives:To explore whether time to diagnosis, time to treatment initiation and age to reach disability milestones has changed in patients with clinically isolated syndrome (CIS) according to different multiple sclerosis (MS)-diagnostic criteria periods.Methods:Retrospective study based on data prospective collected from the Barcelona-CIS cohort between 1994 and 2020. Patients were classified into five periods according to different MS criteria, and the time to MS diagnosis and treatment initiation were evaluated. The age at which MS patients reached an EDSS ≥3.0 was assessed by Cox regression analysis according to diagnostic criteria periods. Finally, in order to remove the classical “Will Rogers” phenomenon by which the use of different MS criteria over time might result on changes of prognosis, 2017 McDonald criteria were applied and age at EDSS ≥ 3.0 was also assessed by Cox regression.Results:1174 patients were included. The median time from CIS to MS diagnosis, and from CIS to treatment initiation showed a 77% and 82 reduction from the Poser to the McDonald 2017 diagnostic criteria periods, respectively. Patients of a given age diagnosed in more recent diagnostic criteria periods had a lower risk of reaching EDSS ≥3.0 than patients of the same age diagnosed in earlier diagnostic periods (reference category Poser period): Adjusted hazard ratio (aHR) 0.47 (95% confidence interval 0.24-0.90) for McDonald 2001, aHR 0.25 (0.12-0.54) for McDonald 2005, aHR 0.30 (0.12-0.75) for McDonald 2010 and aHR 0.07 (0.01-0.45) for McDonald 2017. Early-treatment patients displayed an aHR of 0.53 (0.33-0.85) of reaching age at EDSS ≥3.0 compared to late-treatment. Changes in prognosis together with early-treatment effect were maintained after excluding possible bias derived from the use of different diagnostic criteria over time (so called, “Will Rogers” phenomenon)Conclusion:A continuous decrease in the time to MS diagnosis and treatment initiation were observed across diagnostic criteria periods. Overall, patients diagnosed in more recent diagnostic criteria periods displayed a lower risk of reaching disability. Importantly, the prognostic improvement is maintained after discarding the “Will Rogers” phenomenon, and early treatment appears to be the most likely contributing factor.

The Will Rogers phenomenon, breast cancer and race

Background The Will Rogers phenomenon [WRP] describes an apparent improvement in outcome for patients’ group due to tumor grade reclassification. Staging of cancers is important to select appropriate treatment and to estimate prognosis. The WRP has been described as one of the most important biases limiting the use of historical cohorts when comparing survival or treatment. The main purpose of this study is to assess whether the WRP exists with the move from the AJCC 7th to AJCC 8th edition in breast cancer [BC] staging, and if racial differences are manifested in the expression of the WRP. Methods This is a retrospective analysis of 300 BC women (2007–2017) at an academic medical center. Overall survival [OS] and disease-free survival [DFS] was estimated by Kaplan-Meier analysis. Bi and multi-variate Cox regression analyses was used to identify racial factors associated with outcomes. Results Our patient cohort included 30.3% Caucasians [Whites] and 69.7% African-Americans [Blacks]. Stages I, II, III, and IV were 46.2, 26.3, 23.1, and 4.4% of Whites; 28.7, 43.1, 24.4, and 3.8% of Blacks respectively, in anatomic staging (p = 0.043). In prognostic staging, 52.8, 18.7, 23, and 5.5% were Whites while 35, 17.2, 43.5, and 4.3% were Blacks, respectively (p = 0.011). A total of Whites (45.05% vs. 47.85%) Blacks, upstaged. Whites (16.49% vs. 14.35%) Blacks, downstaged. The remaining, 38.46 and 37.79% patients had their stages unchanged. With a median follow-up of 54 months, the Black patients showed better stage-by-stage 5-year OS rates using 8th edition compared to the 7th edition (p = 0.000). Among the Whites, those who were stage IIIA in the 7th but became stage IB in the 8th had a better prognosis than stages IIA and IIB in the 8th (p = 0.000). The 8th showed complex results (p = 0.176) compared to DFS estimated using the 7th edition (p = 0.004). Conclusion The WRP exists with significant variability in the move from the AJCC 7th to the 8th edition in BC staging (both White and Black patients). We suggest that caution needs to be exercised when results are compared across staging systems to account for the WRP in the interpretation of the data.

The Will Rogers phenomenon, Breast Cancer and Race

Background: The Will Rogers phenomenon [WRP] describes an apparent improvement in outcome for patients’ group due to tumor grade reclassification. Staging of cancers is important to select appropriate treatment and to estimate prognosis. The WRP has been described as one of the most important biases limiting the use of historical cohorts when comparing survival or treatment. The main purpose of this study is to assess whether the WRP exists with the move from the AJCC 7th to AJCC 8th edition in breast cancer [BC] staging, and if racial differences are manifested in the expression of the WRP.Methods: This is a retrospective analysis of 300 BC women (2007- 2017) at an academic medical center. Overall survival [OS] and disease-free survival [DFS], estimated by Kaplan-Meier analysis. Bi and multi-variate Cox regression analyses, used to identify racial factors associated with outcomes.Results: Our patient cohort included 30.3% Caucasians [C] and 69.7% African-Americans [AA]. Stages I, II, III, and IV were 46.2%, 26.3%, 23.1%, and 4.4% of C; 28.7%, 43.1%, 24.4%, and 3.8% of AA respectively, in anatomic staging (p=0.043). In prognostic staging, 52.8%, 18.7%, 23%, and 5.5% were C while 35%, 17.2%, 43.5%, and 4.3% were AA, respectively (p=0.011). A total of C (45.05% vs. 47.85%) AA, upstaged. C (16.49% vs. 14.35%) AA, down-staged. Remaining, 38.46% and 37.79% patients had their stages unchanged.With a median follow-up of 54 months, the AA patients showed better stage-by-stage 5-year OS rates using 8th edition compared to the 7th edition (p=0.000). Among the C, those who were stage IIIA in the 7th but became stage IB in the 8th had a better prognosis than stages IIA and IIB in the 8th (p=0.000). The 8th showed complex results (p=0.176) compared to DFS estimated using the 7th’s (p=0.004).Conclusion: The WRP exists with significant variability in the move from the AJCC 7th to the 8th edition in BC staging (both C and AA patients). We suggest that caution needs to be exercised when results are compared across staging systems to account for the WRP in the interpretation of the data.