Systemic Treatment Initiation in Classical and Endemic Kaposi's Sarcoma: Risk Factors and Global Multi-State Modelling in a Monocentric Cohort Study

Abstract

Background: Although several studies described the clinical course of epidemic and post-transplant Kaposi's Sarcoma (KS), the lack of large cohorts of classic/endemic KS, precluded such characterization.

Methods: We used multi-state modelling in a retrospective monocentric study to evaluate global disease evolution and identify risk factors for systemic treatment (ST) initiation. 160 classic/endemic KS patients consecutively diagnosed between 1990 and 2013 were included.

Results: 41.2% of classic/endemic KS patients required ST. Cumulative incidence of ST after 2 years of follow-up was 28.4% [95% CI: 20.5; 35.5]. Multivariate analysis identified six risk factors for ST initiation: time between first symptoms and diagnosis ≥1 year, endemic KS, total number of lesions ≥10, visceral, head or neck localization and presence of edema. Type of ST, type of KS, age and time between diagnosis and ST were not associated with response. Mean treatment-free time during the first 5 years following ST was 44 months for interferon and 44.6 months for chemotherapy treated patients (Mean difference: -0.5 months [95% CI: -9.5; 4.9]).

Conclusions: Our study reveals ST risk factors in classic/endemic KS and highlights the clinical aggressiveness of the endemic KS subtype. No efficacy difference was observed between standard of care treatments, enabling treatment choice based on patient's fitness.

Keywords: chemotherapy; classical and endemic Kaposi Sarcoma; interferon; multi-state modelling; systemic treatment; treatment free interval.

Figure A1

Lollipop plot representing treatment course of the 66 classic/endemic KS patients who received systemic treatment. Each line represents a single patient. Treatment course is represented during the first five years of follow-up. Treatment free periods are represented by a grey line while treatment intervals correspond to green, red or blue boxes when patients are treated with interferon, chemotherapy or other regimens respectively.

Figure 1

Cumulative Incidence of systemic treatment initiation in classic/endemic KS patients. Dashed lines correspond to the 95% Confidence Interval (CI). The inset table reports the cumulative incidences (IncCum) at 1, 2, 4 and 6 years after KS diagnosis, with their 95% CI.

Figure 2

Cumulative Incidence of systemic treatment initiation in classic/endemic KS patients according to: time between first symptoms and diagnosis (a), KS subtype (endemic vs. classic) (b), total number of lesions (c), visceral localization (d), head/neck localization (e), or presence of lymphedema (f).

Figure 2

Cumulative Incidence of systemic treatment initiation in classic/endemic KS patients according to: time between first symptoms and diagnosis (a), KS subtype (endemic vs. classic) (b), total number of lesions (c), visceral localization (d), head/neck localization (e), or presence of lymphedema (f).

Figure 3

Best overall response after first line of systemic treatment in classic/endemic KS patients, according to type of therapy. Chemo: chemotherapy. CR: Complete Response. PR: Partial Response. SD: Stable Disease. PD: Progressive Disease.

Figure 4

Treatment free time after systemic treatment initiation in classic/endemic KS. This figure was generated using state occupation probabilities: the area under the curve represents the mean time spent alive, on treatment and alive treatment-free during the first 5 years following the initiation of first systemic treatment. The inset table reports the mean times spent treatment free during the first year and the first 5 years following the initiation of first systemic treatment in the whole cohort, with their 95% CI. Dotted lines correspond to 1 and 5 years after first treatment.

Figure 5

Treatment free time after systemic treatment initiation in classic/endemic KS patients stratified according to KS subtype: classic (a) or endemic (b), or according to type of first line treatment: interferon (c) or chemotherapy (d). This figure was generated using state occupation probabilities: the area under the curve represents the mean time spent alive, on treatment and alive treatment-free during the first 5 years following the initiation of first systemic treatment. Dotted lines correspond to 1 and 5 years after first treatment initiation.