Abstract
Simple SummaryConcurrent chemo-radiotherapy is the standard treatment in anal cancer. Intensity-modulated radiotherapy (IMRT) was proved to reduce severe, acute and late toxicities. Moreover, IMRT techniques allow for the planning and delivery of a simultaneous integrated boost (SIB), with a differential dose per fraction given to selected sub-regions during the same treatment session. This boost modality provides the chance to employ a dose-painted approach with a reduction in overall treatment time that could result in a potential clinical advantage. Since a large variability in dose prescription to the primary tumor and elective or involved lymph nodes can be found in available guidelines and clinical practice, a multicenter analysis was conducted to evaluate the pattern of care and the impact of radiotherapy parameters on clinical outcomes for anal cancer patients treated with IMRT techniques within a national cohort.A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.
Highlights
The primary aim of curative chemo-radiotherapy (CRT) for stage II-III anal cancer (AC)patients is to achieve locoregional control, while preserving the anal sphincter with intact function and avoiding a colostomy, with a reasonable quality of life
The 2, 3- and 5-year overall survival (OS) rates were 92.3%, 88.1% and 82.9%, with 2- and 3-year progressionfree survival (PFS) rates of 83.2% and 80.2%, respectively (Figure 1b)
We evaluated age, gender, Eastern Cooperative Oncology Group (ECOG) performance status (PS), human papilloma virus (HPV) and human immunodeficiency virus (HIV) status, clinical stage (T1-T2 vs. T3-T4), lymph node involvement (N0 vs. N+), histological grade (G1-G2 vs. G3), and treatment parameters, such as total dose and treatment duration
Summary
The primary aim of curative chemo-radiotherapy (CRT) for stage II-III anal cancer (AC)patients is to achieve locoregional control, while preserving the anal sphincter with intact function and avoiding a colostomy, with a reasonable quality of life. Since definitive CRT showed a high rate of clinical complete response (cCR up 80–90%) and local control Curative CRT is reported to be associated with a considerable rate of acute toxicities that could require treatment breaks with a prolonged overall treatment time (OTT), potentially affecting clinical outcomes [10,11]. Conformal radiation modalities, such as intensity-modulated radiation therapy (IMRT), may reduce radiation dose to normal tissue with decreased toxicity and similar locoregional control rates [12,13]. In a large retrospective analysis of 151 patients with AC treated with IMRT, an LC rate of 87% at 3 years was reported with low grade ≥3 acute gastrointestinal (GI) (11%) and skin (20%) toxicities [14]. IMRT offers the possibility to deliver a simultaneous integrated boost (SIB), with the chance to give different doses to treatment volumes in the same number of fractions, allowing a safe administration of higher doses to the gross tumor volume (GTV) and with a reduced
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