Experience with Proton Radiotherapy for Anal Canal Carcinoma in Real Czech Practice

Objectives and Course of the Study, Evaluated Patient Population

The primary objective of the retrospective analysis of a cohort of patients treated at the Proton Therapy Center in Prague was to evaluate the efficacy of combining chemotherapy with pencil beam scanning proton radiotherapy in the treatment of anal canal carcinoma. Secondary objectives included the assessment of acute and chronic toxicity and the rate of colostomy necessity.

The analysis included data from 39 patients with confirmed squamous anal carcinoma treated from February 2014 to August 2021.

In all patients, two volumes were irradiated. The first included the tumor and affected lymph nodes (total dose 57.5 GyE) and the second included the regional lymph nodes (total dose 45 GyE). Both volumes were irradiated in 25 fractions, 5 fractions per week (simultaneous integrated boost).

All patients received concomitant chemotherapy with a combination of cisplatin and 5-fluorouracil or capecitabine.

The treatment effect was evaluated by physical examination per rectum and magnetic resonance imaging 8 weeks after completion. Subsequent checks were conducted at 3-month intervals (examination per rectum) and annually (magnetic resonance imaging).

Results

All monitored patients completed the treatment, 76.9% without the need for interruption. The median duration of therapy was 35 days, and the median follow-up time was 30 months. At the time of analysis, 34 patients from this cohort were alive; 2 of the 5 recorded deaths were unrelated to the primary disease. According to Kaplan-Meier analysis, 2-year survival was 94.2%, relapse-free survival was 93.8%, and colostomy-free survival was 91%.

Complete tumor regression was achieved in 36 patients (92.3%), partial regression was observed in 2 patients, and 1 patient experienced tumor progression immediately after treatment. A rescue colostomy was indicated in 2 patients with partial regression due to severe chronic dermatological toxicity.

Grade 3 hematologic toxicity occurred in 7.7% of patients, and grade 4 in 5.1%. The most frequently observed acute non-hematologic toxicities of grade 3-4 included dermatitis (23.1%), diarrhea (7.7%), and dehydration (7.7%). Chronic toxicity manifested mainly as skin atrophy or ulceration (grade 2 in 26.5% of patients, grade 3-4 in 5.8%) and radiation proctitis (grade 2 in 38.2%, grade 3 in 2.9%).

Conclusion and Discussion

Experience from the Proton Therapy Center in Prague demonstrated the high efficacy of pencil beam scanning proton radiotherapy in patients with anal canal carcinoma. A high rate of complete tumor regressions was achieved with a low incidence of acute grade 3-4 hematologic toxicity.

All acute adverse reactions in patients completely resolved, with no deaths attributed to them, and these reactions did not necessitate colostomy. Instead, rescue surgery was required in patients with chronic manifestations of toxicity (skin ulceration, perirectal fistula, and fibrosis).

The complex question remains to what extent pencil beam scanning proton radiotherapy can prevent chronic toxicity. A longer follow-up period of treated patients is necessary for a definitive conclusion.

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Source: Vítek P., Kubeš J., Vondráček V. et al. Pencil beam scanning (PBS) intensity-modulated proton therapy (IMPT) chemoradiotherapy for anal canal cancer – single institution experience. Cancers (Basel) 2021; 14 (1): 185, doi: 10.3390/cancers14010185.