Abstract
Background
Prior studies have demonstrated improved disease-specific survival of mycosis fungoides (MF) patients over the last 50 years.
Objective
To analyse patterns of survival and incidence from 1973 to 2016 and determine whether apparent improvements in MF-specific survival are due to lead-time bias rather than improvements in treatment.
Methods
We performed an analysis of 10 155 patients diagnosed with MF from 1973 to 2016 in the United States cancer registries of SEER-18. We also performed a literature review of papers including stage data for unselected populations of MF patients prior to 2000.
Results
Incidence of MF increased from 3.0 per million person-years in the 1970s to 5.9 in the 2010s. For all cohorts, non-Hodgkin lymphoma (including MF) was the leading cause of death. Survival analysis demonstrated marked improvement in disease-specific and overall survival from the 1970s to 2010s. Based on systematic review of the literature, 32%–73% of patients diagnosed prior to 2000 were diagnosed with early-stage disease, as opposed to 81% of patients in the SEER 2000–2016 cohort (P < 0.035 for all cohorts).
Conclusions
Although there have been improvements in MF-related survival over the last 50 years, these may reflect improvements in our ability to diagnose early-stage disease rather than improved treatment.
Introduction
Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, accounting for approximately 40% of all cutaneous lymphomas and 54%–65% of CTCLs.1,2
Prior studies have demonstrated increases in incidence and survival since 1969.1,3–5 While the overall incidence of MF in the United States has stabilized at approximately 4.0 cases per million persons per year.1,3,6,7 In the UK, data from Public Health England’s 2016 report yielded an overall incidence of 3.7 per million persons per year.8 MF generally has a favourable prognosis, with an overall 5-year survival between 79% and 92%.3 Since 1973, there appears to have been a steady increase in relative survival.5
Many changes have occurred in the diagnosis and treatment of MF over the last 50 years. Diagnostics in the 1980s and 1990s underwent the seismic shifts with the development of immunohistochemistry and polymerase chain reaction for T-cell receptor (TCR) gene rearrangements, facilitating diagnosis of MF at earlier stages.9 Therapies have evolved from cytotoxic chemotherapy in the 1970s to monoclonal antibodies and hematopoietic stem cell transplantation in the 2000s. It is difficult to assess which of these advances may be driving the improvements in survival for patients with MF seen over the last 50 years. In addition, accurate assessment of our historic progress is of great importance in measuring future success.
We seek to provide an interim update of the incidence and mortality trends in MF. Further, we intend to use Surveillance, Epidemiology and End Results (SEER) data and a systemic literature review to assess whether improvements in survival rates may be in part due to lead-time bias due to earlier detection of MF cases in the last several decades. Data regarding staging are available in SEER for patients diagnosed after 2000; a systematic review is necessary to assess stage at diagnosis prior to 2000. We also seek to analyse patterns of utilization of chemotherapy and radiation therapy for treatment of this cutaneous lymphoma and to analyse changes in causes of death over the last 50 years and by stage.
Methods
Patients with MF diagnosed between 1973 and 2016 were identified in the 18 SEER cancer registries [SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2018 Sub (1973–2016)] via ICD-O-3 code 9700/3; Sezary syndrome was excluded. In analysis of cause of death, all deaths due to non-Hodgkin lymphoma were considered attributable to MF.
Age-adjusted incidence rates of MF were calculated via the SEER★Stat software package, v. 8.3.4 (National Cancer Institute, Bethesda, MD, USA), using the SEER 9 Regs Research Data, Nov 2018 Sub (1975–2016) <Katrina/Rita Population Adjustment>. Age-adjusted rates were calculated for race (White/Black/other) and gender by decade.
Routine methods of categorical (chi-square test) and continuous (Student’s t-test and ANOVA) testing were applied with statistical significance defined at α level 0.05. Plots and summary measures were conducted in R (version 3.4; The R Foundation, Vienna, Austria). Kaplan–Meier survival analyses were performed in SAS (version 8; SAS Institute Inc., Cary, NC, USA).
Stage data are only available in SEER after 2000. To assess stage data prior to 2000, a systematic literature review was performed using the terms ‘mycosis fungoides epidemiology’, ‘mycosis fungoides demographics’, ‘mycosis fungoides cohort’, ‘CTCL epidemiology’, ‘CTCL demographics’, and ‘CTCL cohort’ in PubMed and Embase to identify all papers published before 2000. This was performed on 31 August 2019. This returned 513 manuscripts in PubMed and 141 in Medline. Articles containing descriptive demographic data for unselected cohorts of >20 patients, including stage information (either via description of stage, physical phenotype or TNM classification),10 containing data from prior to 2000 were selected for inclusion. Clinical trials were excluded to minimize selection bias as patients in clinical trials may have higher stage disease. Manuscripts were reviewed by authors AG and KG; any disagreements were mediated by DO. This yielded seven manuscripts. Data collected included age, race, gender and stage information; race was available for only 3 of 7 studies. Stage was converted to conform to the International Society for Cutaneous Lymphomas (ISCL) and European Organization of Research and Treatment of Cancer (EORTC) guidelines presented in Kim et al.11 Patients were classified as early (stage IA–IIA) or late (stage IIB+). For cases where only descriptive information was provided, patch and plaque were classified as early, tumour or erythrodermic as late. Due to the heterogeneity of the populations examined in each study and the variability of reporting of stage data, meta-analysis was not performed.
This study was exempt from Institutional Review Board approval.
Results
Demographics
We identified 10 155 patients diagnosed with MF from 1973 to 2016. The median age decreased from 1973–1999 to 2000–2016 (median 62.5 and 60 years, respectively, Table 1). MF was more common in males than in females during all time periods; however, the ratio of males to females decreased from 1.9 in the 1970s to 1.4 after 1990. Median follow-up was significantly shorter for the 2010–2016 cohort compared to prior to 2010 (P = 0.0032). Across all time periods, the majority of patients were White, followed by Black, then Hispanic and then Asian/Pacific Islander. From the 1970s to 2010s, there was a decrease in the percentage of White patients (79% vs. 60% respectively) and a concomitant increase in the percentage of Hispanic patients (4% vs. 11%, respectively). The percentage of Black patients remained roughly stable (13% vs. 15%).
Table 1.
Demographics, causes of death and survival for patients with MF from 1973 to 2016
| 1973–1979 | 1980–1989 | 1990–1999 | 2000–2009 | 2010–2016 | |
|---|---|---|---|---|---|
| Incidence per 1 000 000 person-years (95% CI) | 3.0 (2.7–3.4) | 4.7 (4.4–5.0) | 5.3 (5.0–5.6) | 5.9 (5.6–6.2) | 5.8 (5.5–6.2) |
| N | 269 | 937 | 1630 | 3846 | 3473 |
| Median age at diagnosis (range) | 63 (21–89) | 62 (6–98) | 62 (5–101) | 59 (2–98) | 60 (0–103) |
| Median follow-up, months (range) | 114 (0–502) | 135.5 (0–440) | 180 (0–323) | 111 (0–203) | 31 (0–83) |
| Sex | |||||
| Male (%) | 175 (65) | 558 (60) | 946 (58) | 2186 (57) | 2006 (58) |
| Female (%) | 94 (35) | 379 (40) | 684 (42) | 1660 (43) | 1467 (42) |
| Ratio of M : F | 1.9 | 1.5 | 1.4 | 1.4 | 1.4 |
| Ethnicity | |||||
| White (%) | 213 (79) | 736 (79) | 1113 (68) | 2514 (65) | 2069 (60) |
| Black (%) | 36 (13) | 116 (12) | 238 (14) | 537 (14) | 531 (15) |
| Asian/Pac Island (%) | 6 (2) | 38 (4) | 104 (6) | 246 (6) | 244 (7) |
| Native American (%) | 2 (0.7) | 2 (0.2) | 10 (0.6) | 15 (0.4) | 18 (0.5) |
| Other (non-Hispanic) (%) | 2 (0.7) | 8 (0.8) | 39 (0.2) | 159 (4) | 218 (6) |
| Hispanic (%) | 10 (4) | 37 (0.4) | 126 (7) | 375 (10) | 393 (11) |
| Causes of death | |||||
| Alive (% of total) | 27 (10) | 175 (19) | 687 (42) | 2540 (66) | 3059 (88) |
| Deceased (% of total) | 242 (90) | 762 (81) | 943 (58) | 1306 (34) | 414 (12) |
| NHL (% of deceased) | 86 (35) | 216 (28) | 226 (23) | 497 (38) | 213 (51) |
| Other malignancy (% of deceased) | 41 (17) | 136 (18) | 183 (19) | 254 (19) | 63 (15) |
| Infectious (% of deceased) | 14 (6) | 44 (6) | 62 (7) | 43 (3) | 14 (3) |
| Pulmonary (% of deceased) | 7 (3) | 23 (3) | 33 (3) | 40 (3) | 0 (0) |
| Cardiovascular (% of deceased) | 53 (22) | 171 (22) | 223 (24) | 187 (14) | 48 (12) |
| Liver (% of deceased) | 2 (1) | 5 (1) | 4 (0) | 4 (0) | 2 (0) |
| Neurologic (% of deceased) | 16 (7) | 42 (6) | 66 (7) | 70 (5) | 10 (2) |
| Renal (% of deceased) | 0 (0) | 7 (1) | 9 (1) | 14 (1) | 4 (1) |
| Diabetes mellitus (% of deceased) | 0 (0) | 13 (0) | 14 (0) | 16 (0) | 7 (0) |
| Various† (% of deceased) | 23 (10) | 105 (14) | 123 (13) | 177 (14) | 47 (11) |
| Treatment | |||||
| Radiation (%) | 111 (41) | 288 (31) | 209 (13) | 346 (9) | 278 (8) |
| Chemotherapy (%) | 123 (45) | 432 (46) | 516 (32) | 759 (20) | 573 (16) |
| Overall survival | |||||
| 2-year OS (95% CI) | 0.84 (0.80, 0.89) | 0.84 (0.80, 0.89) | 0.89 (0.87, 0.91) | 0.91 (0.90, 0.92) | 0.91 (0.90, 0.92) |
| 5-year OS (95% CI) | 0.66 (0.61, 0.72) | 0.66 (0.61, 0.72) | 0.77 (0.75, 0.79) | 0.81 (0.79, 0.82) | 0.81 (0.79, 0.83) |
| 10-year OS (95% CI) | 0.49 (0.43, 0.55) | 0.49 (0.43, 0.55) | 0.63 (0.61, 0.65) | 0.69 (0.68, 0.71) | |
| 15-year OS (95% CI) | 0.39 (0.33, 0.45) | 0.39 (0.33, 0.45) | 0.52 (0.50, 0.55) | 0.58 (0.55, 0.60) | |
| Disease-specific survival | |||||
| 2-year DSS (95% CI) | 0.75 (0.67, 0.84) | 0.80 (0.76, 0.84) | 0.91 (0.90, 0.93) | 0.94 (0.93, 0.95) | 0.95 (0.94, 0.96) |
| 5-year DSS (95% CI) | 0.54 (0.45, 0.64) | 0.64 (0.59, 0.69) | 0.84 (0.82, 0.87) | 0.88 (0.87, 0.89) | 0.90 (0.88, 0.91) |
| 10-year DSS (95% CI) | 0.40 (0.32, 0.50) | 0.54 (0.49, 0.59) | 0.79 (0.76, 0.82) | 0.84 (0.83, 0.85) | |
| 15-year DSS (95% CI) | 0.32 (0.25, 0.42) | 0.49 (0.45, 0.55) | 0.77 (0.74, 0.80) | 0.81 (0.80, 0.83) | |
Asian/Pac Island, Asian or Pacific Islander; CI, confidence interval; DSS, disease-specific survival; F, female; M, male; OS, overall survival.
Various includes accidents and adverse events; congenital anomalies; homicide and legal intervention; other cause of death; no cause of death; suicide and self-inflicted injury; and symptoms signs, and ill-defined conditions.
Incidence
Incidence of MF increased from 3.0 per million person-years in the 1970s to 5.9 in the 2010s (Table 1).
Survival
Kaplan–Meier overall survival (OS) and disease-specific survival (DSS) curves (Fig. 1), and the 2-, 5-, 10- and 15-year OS and DSS (Table 1) demonstrate improvement in OS and DSS with each decade. For generation of DSS analysis, it was necessary to assume that all deaths due to NHL were due to MF. However, 93 of the 1238 patients who died due to NHL had developed a second NHL; it is not possible to determine from SEER data which malignancy these patients died of (MF vs. their second NHL). These patients cannot be excluded from the data set.
Figure 1.
Survival curves. (a) Overall survival for patients with MF by decade. (b) Disease-specific survival for patients with MF by decade.
Causes of death
For all cohorts, NHL was the leading cause of death (Table 1). Of the cohorts from 1973 to 1999, cardiovascular disease was the second most common cause of death, whereas for the 2000–2016 cohorts, another malignancy (other than NHL) was the second most common cause of death. When patients from 2000 to 2016 are stratified based on stage, patients of all disease stages were most likely to die of NHL. The second most common cause of death for all stages during that time period was other malignancy (Table 2).
Table 2.
Cause of death by stage (2000–2016)
| IA | IB | IIA | IIB | III | IV | |
|---|---|---|---|---|---|---|
| N | 2658 | 634 | 67 | 252 | 194 | 260 |
| Alive (% of total) | 2274 (86) | 526 (83) | 39 (59) | 158 (63) | 102 (53) | 156 (60) |
| Deceased (% of total) | 384 (14) | 108 (17) | 28 (42) | 94 (37) | 92 (47) | 104 (40) |
| NHL (% of deceased) | 126 (33) | 51 (47) | 20 (72) | 59 (63) | 59 (64) | 76 (73) |
| Other malignancy (% of deceased) | 85 (22) | 18 (17) | 1 (4) | 10 (11) | 6 (7) | 12 (12) |
| Infectious (% of deceased) | 19 (5) | 3 (3) | 1 (4) | 1 (1) | 2 (2) | 3 (3) |
| Pulmonary (% of deceased) | 6 (2) | 2 (2) | 1 (4) | 2 (2) | 0 (0) | 0 (0) |
| Cardiovascular (% of deceased) | 61 (16) | 14 (13) | 2 (7) | 6 (6) | 10 (11) | 3 (3) |
| Liver (% of deceased) | 3 (1) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Neurologic (% of deceased) | 20 (5) | 3 (3) | 2 (7) | 4 (4) | 2 (2) | 1 (1) |
| Renal (% of deceased) | 3 (1) | 0 (0) | 0 (0) | 0 (0) | 2 (2) | 1 (1) |
| Diabetes mellitus (% of deceased) | 2 (2) | 2 (4) | 0 (0) | 2 (3) | 2 (3) | 1 (1) |
| Various† (% of deceased) | 59 (15) | 15 (14) | 1 (4) | 10 (11) | 9 (10) | 7 (7) |
NHL, non-Hodgkin lymphoma.
Various includes accidents and adverse events; congenital anomalies; homicide and legal intervention; other cause of death; no cause of death; suicide and self-inflicted injury; and symptoms signs, and ill-defined conditions
Chemotherapy and radiation
Over the period from 1973 to 2016, there was a steady decline in the proportion of patients treated with chemotherapy and radiation, from 45% and 41%, respectively, in the 1970s to 8% and 16% in the 2010s. All patients who received radiation received beam radiation. Chemotherapy regimens are not specified in SEER.
Historic stage
Stage information was available in SEER for patients from 2000 to 2016 (Table 3). A systematic review was conducted to assess the distribution of patients by stage at the time of diagnosis prior to 2000 and identified seven papers, with cohorts from the United States (4), UK (1), Italy (1) and Australia (1). While only 32%–73% of patients diagnosed prior to 2000 were diagnosed with early-stage disease. 81% of patients in the SEER 2000–2016 cohort (P < 0.035 for all cohorts). Three papers contained race information; all three had a higher proportion of White patients than the 2000–2016 cohort (P < 0.02). There was a male predominance in all cohorts. Data were insufficient to compare age distributions. Meta-analysis was not performed due to inability to adequately assess heterogeneity of the populations in the papers.
Table 3.
Stage data
| Years | Source | N | M : F ratio | White (W), Black (B), Other (O), % |
Median age (range) | Stage data format | Early stage (IA–IIA) (%) | Advanced stage (IIB+) (%) | P value† | |
|---|---|---|---|---|---|---|---|---|---|---|
| This study | 2000–2016 | SEER, US | 4077 | 1.4 | W 4583 (62) B 1068 (15) O 1668 (23) |
59.5 (0–103) | Stage IA–IVB | 3302 (81) | 775 (19) | |
| Lamberg et al., 197932 | 1974–1977 | MF Cooperative Group, US | 367 | 1.9 | W 301 (82) B 39 (11) O 7 (2) |
58.2 | TNM | 155 (46) | 184 (54) | <0.00001 |
| Redmond et al., 197933 | 1965–1976 | Wayne State Univ. of Med., US | 90 | 1.7 | W 84 (93) B 5 (6) O 1 (1) |
52 (3–82) | Morphologic description | 63 (70) | 27 (30) | 0.009 |
| Olsen et al., 198435 | 1966–1981 | Duke, US | 63 | 1.2 | B 50 (80) W 13 (20) O 0 (0) |
58.8 | Stage I–IV | 26 (46) | 30 (54) | <0.00001 |
| Mazza et al., 198536 | 1973–1982 | Universita di Bologna, Italy | 45 | 2.0 | — | 60 (26–80) | Morphologic description | 24 (53) | 21 (47) | <0.00001 |
| Slevin et al., 198737 | 1963–1982 | Christie Hospital, UK | 85 | 1.9 | — | 64 (19–95) | TNM | 36 (49) | 38 (51) | <0.00001 |
| Sausville et al., 198834 | 1975–1987 | NCI, NIH, US | 152 | 1.9 | — | — | Stage IA–IVB | 49 (32) | 103 (68) | <0.00001 |
| Yen et al., 199738 | 1977–1995 | St. Vincent’s, Australia | 107 | 1.4 | — | 60.4 | Stage IA–IVB | 78 (73) | 29 (27) | 0.036 |
M : F ratio, male:female ratio.
Comparison of stage in this study to prior literature.
Discussion
In this study, we utilized the most recent data from the SEER program to provide an updated, comprehensive analysis of mortality trends in MF over the last 50 years and to assess the role of lead-time bias in apparent improvements in DSS.
We found that patients with MF experienced marked improvements in overall survival (OS) and disease-specific survival (DSS) over the time period from 1973 to 2016. Previous works reporting improvements in survival have hypothesized that these may be due to advancements in MF medical therapy.4,5,12 However, of commonly used MF therapies, only allogeneic hematopoietic stem cell transplant (HSCT) and brentuximab have resulted in significant alteration of the natural history of MF.13–18 The remainder of treatments can largely be seen as palliative. Since brentuximab was only approved for MF in 2016 and HSCT is not widely used, we hypothesized that improving survival rates may be attributable in part due to lead-time bias.
Advances in immunohistochemistry19–23 and gene rearrangement detection technology24–27 in the 1980s and 1990s have improved our ability to differentiate early MF from other inflammatory diseases, resulting in improved ability to diagnose early-stage MF. This may in turn have yielded an observed improvement in survival rate, an example of lead-time bias. To test the lead-time bias hypothesis, we carried out a formal literature review which identified 7 population-based studies from 1979 to 1997. Patients diagnosed between 2000 and 2016 were significantly more likely to be diagnosed with early-stage (IA–IIA) disease compared to those diagnosed prior to 1997 (80% vs. 50%, P < 0.0001). This supports the hypothesis that improvements in survival may be at least partially due to lead-time bias. Notably, there is minimal difference in DSS between the 2000s and 2010s; there were no major paradigmatic changes in diagnosis or treatment of MF during that time period.
Other potential sources of improvement in survival include improvement in overall survival due to improvements in treatment of cardiovascular, pulmonary and endocrine diseases over the last 50 years; however, we saw improvements in both MF-specific and overall survival. Improvements in infection control and antibiotic therapies may also be a significant contributor – many patients with reported NHL-associated death may have actually died of infections due to damaged skin barrier, recurrent hospitalizations and immunosuppressive therapies. Better infection control, wound care and antibiotic therapies may result in less mortality amongst MF patients. Finally, changes in CTCL classification and diagnostic capabilities may play a role, with the splitting of Sezary syndrome and other aggressive CTCLs from MF.
Analysis of cause of death revealed that across all time periods and all stages, patients with MF are most likely to die of their MF. This is consistent with the report by Kim et al. However, that report did not parse cause of death beyond ‘due to MF’ and ‘not due to MF’. It is important to note that patients in the 2000–2009 and 2010–2016 cohorts have had less time to die from non-MF causes, such as cardiovascular or pulmonary disease, which are largely diseases of the elderly. This may explain why prior to 2000 the second most common cause of death was cardiovascular disease, but from 2010 to 2016 other malignancy became the second most common. Overall, this analysis provides important information for counselling patients on the risks they face upon receiving a diagnosis of MF.
Stratification of cause of death by stage for patients diagnosed between 2000 and 2016 revealed that although patients with early-stage disease have excellent survival, the most common cause of death for all stages is NHL (MF). This does run counter to the popular description of MF as ‘a disease you die with, not die from’. As stage increases, risk of death due to NHL increases. The second most common cause of death in for all stages is other malignancy. Risk of death due to cardiovascular cause is highest in early-stage disease and declines as the competing risk of MF mortality increases.
We observed a progressive decline in the use of both radiation and chemotherapy in treatment of MF through the decades. Decline in use of chemotherapy over that time period may reflect changes in stage of diagnosis of MF (i.e. patients diagnosed at earlier stage, as detailed above, are less likely to need chemotherapy). Over the last several decades, there has also been increasing recognition that relapse is common with cytotoxic chemotherapy.13 New immunotherapy and biologics are set to hopefully revolutionize MF treatment, but they have not been on the market long enough for their effects to be reflected in SEER data.
Although there has been a decline in the use of conventional cytotoxic drugs during this time period, the last 10 years have seen the advent of numerous new therapies, including antibody–drug conjugates like brentuximab vedotin, diphtheria toxin conjugates like denileukin diftitox and monoclonal antibodies such as alemtuzumab. The majority of these novel agents are too new for their effects to be seen in SEER data for the last decade, but given the excellent response seen in some clinical trials, we anticipate that drugs like brentuximab may make substantial inroads in improving MF survival.18 Bexarotene, an RXR-receptor antagonist, was approved in the United States for the treatment of early-stage MF in 1999. However, bexarotene, like other treatment modalities including combination chemotherapy, has been unable to demonstrate durable disease control or alteration of survival.13
Decline in the use of radiotherapy may largely be due to the patterns of practice amongst dermatologists who may be less likely to refer patients for radiation. Our study detailed an absolute decrease of 25% from the 1970s to the 2010s. A recent analysis of the NCDB database showed a progressive decline in the use of radiotherapy as first-line treatment for CTCL,28 consistent with our results, despite the fact that it continues to be recommended amongst the first-line treatments by the NCCN.29 This decline follows a parallel in the loss of the use of superficial radiation therapy from the practice umbrella of dermatologists.30 Another possible explanation is that given the indolent nature of this subtype of NHL, managing physicians may choose to omit radiation therapy on the expectation that other topical therapies may be equally effective or that more intensive therapy may provide more durable response.
The most significant limitation of this analysis is that our conclusions regarding lead-time bias and our presentation of possible causes of decreased use of chemotherapy and radiation are speculative. We have endeavoured to provide evidence for the lead-time hypothesis, but it ultimately cannot be definitively proven. In addition, although statistical tools to calculate the impact of lead-time bias do exist, we do not have sufficient information about the pre-2000 cohorts to quantify the impact lead-time bias may have had on survival; this would require case-based information including follow-up and survival, which are not available for historic patients.31
The SEER database offers some limitations. In the SEER database, deaths due to MF are lumped in the broader category of deaths due to NHL. Ninety-three of the 1238 patients who died due to NHL had developed a second NHL; it is not possible to determine whether these patients died of MF or their second NHL. These patients cannot be excluded from the data set. In this study, we assumed that all deaths due to NHL were due to MF.
Our systematic review is limited by the limited data included in each paper; this precluded performance of a meta-analysis. The populations examined in the systematic review papers may have a different demographic distribution than our population. SEER is a US-based database, and an argument could be made that it should only be compared to historical US cohorts due to differences in age and race distribution. When the analysis is limited to only US cohorts, prior to 2000 patients were still more likely to be diagnosed at higher stage (30%–68%) than in SEER from 2000 to 2016 (19%, P < 0.009).32–35
In conclusion, we have provided a population-based study of MF and literature review that support the hypothesis that improved survival of patients with MF over the period of 1973–2016 is due to a lead-time bias rather than improvements in medical therapy. This highlights the importance of new therapies currently in clinical trials and development, as patients with MF need new therapies that alter the natural history of the disease rather than just palliate its symptoms.
Acknowledgements
Research reported in this publication was supported by NIH grant P30 CA77598 utilizing the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. This funded the statistical analysis. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Footnotes
Conflicts of interest
The authors report no conflicts of interest.
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