Outcomes of Patients Living With HIV and Anal Cancer Treated With Definitive Intensity-Modulated Radiation Therapy and 5-Fluorouracil- or Capecitabine-Based Chemotherapy

Abstract

To assess outcomes after definitive chemo-irradiation in HIV patients with anal cancer, and evaluate hemato-immunologic (HI) toxicity by dynamics of CD4+ cell counts and lymphocytes and their association with the dose received by active bone marrow (ABM).Patients treated for anal cancer with HIV infection at a single institution between 2007-2020 were identified. Characteristics were tabulated along with CD4+ cell counts and lymphocytes ranging from before treatment to length of follow-up. Dose to ABM was derived by overlaying the bone contours and 3D dose matrix on a pre-treatment PET/CT scan using deformable registration. Parts of the bone with greater than the mean PET standardized uptake value (SUV) in the bone were designated as ABM. Differences in HI parameters over time points were compared using Wilcoxon rank sum tests; risk of recurrence, overall survival (OS) and progression-free survival (PFS) were modeled using Kaplan-Meier methods.A total of 44 patients with anal cancer and HIV were identified, of which 7 had detectable HIV viral load pre-treatment. Radiation was most commonly 50.4-54 Gy via IMRT; 3 patients underwent RT alone. Chemotherapy was 5-fluorouracil+mitomycin (n = 27), Capecitabine+mitomycin (n = 11), or other (n = 3). With median follow-up 59 months (range: 5-164) there were 7 loco-regional recurrences, 2 distant metastases and 9 deaths. The 2- and 5-year OS for patients with stage I/II disease was 100% and 93.3% vs. 88.1% and 66.6% for stage III, the 2- and 5-year PFS were both 93.8% for stage I/II disease vs. 76.5% and 56.7% for stage III. Outcomes with 5FU vs. capecitabine were comparable with 2-year OS of 92.3% and 90.9% (P = 0.89) and PFS of 77.4% and 90.9% (P = 0.26). CD4 counts dropped from a pre-treatment median of 320 cells/ul to 101 at nadir (after ∼3 months), to 163 at 1 year and 214 at 2 years post IMRT. Lymphocyte counts changed from 1,600 per ul to 400 at nadir, to 1,200 and 1,400 at 1 and 2 years. Patients with distant or locoregional recurrence showed trends (P < 0.10) of worse recovery of HI toxicity at 1 and 2 years (Table 1). Median mean ABM dose was 33.7 Gy (range: 20.2-40.3 Gy) and median V15Gy and V40Gy were 91% (range: 58-99%) and 39% (range: 0-62%). No association was found between ABM dose and dynamics of HI toxicity, possibly due to relatively high ABM doses for all patients.Outcomes after definitive chemo-IMRT were promising with excellent OS and PFS in this vulnerable patient group, with no difference when substituting 5-fluorouracil for capecitabine. There was some acute HI toxicity with worse recovery in patients who experienced disease recurrence and strategies to better spare ABM including dose de-escalation are ongoing.