French multicentre clinical evaluation of helical TomoTherapy® for anal cancer in a cohort of 64 consecutive patients

Abstract

Purpose/ObjectivesTo assess feasibility and toxicity of Helical TomoTherapy® for treating anal cancer patients.MethodsFrom 2007 to 2011, 64 patients were consecutively treated with TomoTherapy® in three centres for locally advanced squamous-cell anal carcinoma (T2 > 4 cm or N positive). Prescribed doses were 45 Gy to the pelvis including inguinal nodes and 59.4 Gy to the primary site and involved nodes with fractions of 1.8 Gy, five days a week. A positional Megavoltage Computed Tomography was performed before each treatment session. All acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events version 3.0. Survival analysis was performed using the Kaplan-Meier method.ResultsMedian follow-up was 22.9 months. Fifty-four women and 10 men were treated (median age: 62 years). Nineteen patients (29.7 %) had T2, 16 patients (25.0 %) T3, and 27 patients (42.2 %) T4 tumours. Thirty-nine patients (60.9 %) had nodal involvement. Median tumour size was 45 mm (range, 10–110 mm). Seven patients had a colostomy before treatment initiation. Fifty-seven patients received concomitant chemotherapy (5-FU/cisplatin or 5-FU/mitomycin-based therapy). Forty-seven patients (73.4 %) experienced a complete response, 13 a partial response or local recurrence, and 11 had salvage surgery; among these, six became complete responders, three experienced metastatic failure, and two local failure. At least four patients experienced metastatic recurrence (concomitant to a local failure for one patient). The two-year overall survival was 85.6 % (95 %CI [71.1 %–93.0 %]), and the one-year disease-free survival, and colostomy-free survival were 68.7 % (95 %CI [54.4 %–79.4]), and 75.5 % (95 %CI [60.7 %–85.3 %]) respectively. Overall survival, disease-free survival and colostomy free-survival were significantly better for women than men (p = 0.002, p = 0.004, and p = 0.002 respectively). Acute grade ≥3 toxicity included dermatologic (46.9 % of patients), gastrointestinal (20.3 %), and hematologic (17.2 %) toxicity. Acute grade 4 hematologic toxicity occurred in one patient. No grade 5 event was observed.ConclusionsTomoTherapy® for locally advanced anal cancer is feasible. In our three centres of expertise, this technique appeared to produce few acute gastrointestinal toxicities. However, high rates of dermatologic toxicity were observed. The therapeutic efficacy was within the range of expectations and similar to previous studies in accordance with the high rates of locally advanced tumours and nodal involvement.

Intensity modulated radiotherapy for anal canal squamous cell carcinoma: A 16-year single institution experience

“…Treatment was associated with favorable oncologic outcomes with 4-year estimates of OS, CFS, PFS, and LRR of 81%, 77%, 78%, and 9%, respectively. Toxicity rates were comparable to other IMRT series (shown in Table 4 ), and importantly, demonstrate improvements relative to historical 3DCRT series [8] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] . Prolonged overall treatment duration was associated with an increased risk of LRR and colostomy while continued tobacco smoking during CRT was associated with an increased risk of acute dermatologic toxicity.…”

“…Interesting aspects of this work include the relatively large patient cohort (n = 127), fairly homogeneous delivery of DP-IMRT (95%), mature median follow-up of 47 months (IQR: 28- 89 months), robust collection of acute and late AEs, and the availability of extensive patient, disease, and treatment characteristics which facilitated an analysis of variables associated with oncologic efficacy outcomes. Our series, in addition to the IMRT series summarized within Table 4, continue to show that IMRT is associated with a favorable toxicity profile compared to historical 3DCRT series [8,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. We identified rates of grade 3+ acute GI, dermatologic, and hematologic toxicity of 17%, 16%, and 31%, respectively.…”

“…The use of IMRT may reduce treatment-related AEs compared with 3-dimensional conformal radiotherapy (3DCRT), thereby supporting its use as the preferred treatment technique [8] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] . For instance, Radiation Therapy Oncology Group (RTOG) 0529 used a dose-painted IMRT (DP-IMRT) technique and demonstrated a reduction in grade 3+ acute gastrointestinal (GI) and dermatologic AEs and grade 2+ hematologic AEs when compared to historical controls treated with 3DCRT [8] .…”

Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE

“…Chemoradiotherapy achieves a good outcome for T1-T2 tumors without nodal involvement, but T3-T4 or N1 tumors are associated with a poorer prognosis (5,6). This therapeutic strategy has remained unchanged since the 1980s but has benefited from major technical advances in imaging (MRI, endoscopic anal ultrasound, and PET-CT) and radiotherapy, particularly with the development of intensity-modulated radiotherapy (IMRT) (7)(8)(9)(10)(11). By conforming the dose to complex clinical target volumes using multiple beams and varying dose rates, IMRT results in minimizing dose to healthy tissues aiming to reduce toxicity while preserving the dose homogeneity to clinical target volumes.…”