The assessment of local response using magnetic resonance imaging at 3- and 6-month post chemoradiotherapy in patients with anal cancer

Abstract

Objectives: To assess the use of MRI-determined tumour regression grading (TRG) in local response assessment and detection of salvageable early local relapse after chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC).

Methods: From a prospective database of patients with ASCC managed through a centralised multidisciplinary team, 74 patients who completed routine post-CRT 3- and 6-month MRIs (2009-2012) were reviewed. Two radiologists blinded to the outcomes consensus read and retrospectively assigned TRG scores [1 (complete response) to 5 (no response)] and related these to early local relapse (within 12 months) and disease-free survival (DFS).

Results: Seven patients had early local relapse. TRG 1/2 scores at 3 and 6 months had a 100 % negative predictive value; TRG 4/5 scores at 6 months had a 100 % positive predictive value. All seven patients underwent salvage R0 resections. We identified a novel 'tram-track' sign on MRI in over half of patients, with an NPV for early local relapse of 83 % at 6 months. No imaging characteristic or TRG score independently prognosticated for late relapse or 3-year DFS.

Conclusions: Post-CRT 3- and 6-month MRI-determined TRG scores predicted salvageable R0 early local relapses in patients with ASCC, challenging current clinical guidelines.

Key points: • Post-chemoradiotherapy MRI (3 and 6 months) helps local response assessment in ASCC. • The MRI-TRG system can be used reproducibly in patients with ASCC. • The TRG system facilitates patient selection for examination under anaesthesia and biopsy. • The use of MRI-TRG predicts for detection of salvageable early local relapses. • The TRG system allows for a standardised follow-up pathway.

Keywords: Anus neoplasms; Carcinoma, squamous cell; Chemoradiotherapy; Magnetic resonance imaging; Tumour response.

Fig. 1

Demonstrative figure showing the normal anal anatomy in row ‘a’ (line diagram representation in left column, high resolution T2W MR in the coronal plane in mid column and in the axial plane in the right hand column). Row ‘b’ demonstrates an upper anal canal tumour involving the left internal sphincter extending from the 2 o’clock to 6 o’clock position (arrows). Post-CRT appearances in row ‘c’ showing the tram track sign as parallel bands of low signal along the inner and outer margins of the left internal sphincter at the site of original tumour (arrows)

Fig. 2

Time to event plot for local relapses after chemoradiotherapy (CRT) shown by early (within 12 months) and late (after 12 months) relapses. Short vertical hashes represent censored events. Markers in upper panel indicate local relapse events: blue, early relapses; orange, late relapses

Fig. 3

Tumour regression grading (TRG) scores on post-treatment magnetic resonance imaging (MRI) correlated with local disease relapse. SCC squamous cell carcinoma

Fig. 4

High resolution coronal T2-weighted images (a, b, d). Baseline magnetic resonance image (MRI) (a), showing an intermediate signal intensity tumour (arrow) in the lower anal canal extending to the verge. The 3-month post-chemoradiotherapy (CRT) MRI (b) shows response to treatment but with mixed low and high signal areas at site of original tumour (arrow), this was considerate indeterminate for residual disease versus inflammation, tumour regression grading (TRG) score 3. Photomicrograph with H & E stain and 20X magnification (c), showing partially organising and inflamed granulation tissue with no viable residual tumour, this correlates with TRG 3 on the post-CRT MRI. The 6-month post CRT MRI (d) now shows improvement in appearances with low signal change and no evidence of any suspicious intermediate signal indicating the previously noted changes due to inflammation had resolved, downgrading the TRG score to 2

Fig. 5

High resolution axial T2-weighted images (a-c). Baseline magnetic resonance image (MRI) (a), showing an intermediate signal intensity tumour (arrows) in the anal canal extending from the 5 o’clock to 11 o’clock position. The 3-month post-chemoradiotherapy (CRT) MRI (b), shows decrease in size but residual intermediate signal remains of concern for tumour (arrow), tumour regression grading (TRG) score 4. The 6-month post CRT MRI (c) shows interval progression with central cavitation of the suspected residual tumour (arrow), TRG score 5. Photomicrograph with H & E stain and 4X magnification showing residual viable invasive squamous cell carcinoma (star shape) associated with some underlying stromal hyalinisation (triangle shape) in response to prior radiotherapy, these histological features correlate with Grades 4 to 5 on the post-CRT MRI. The patient subsequently underwent radical surgery with flap reconstruction

Fig. 6

Proposed patient follow-up pathway based on post-chemoradiotherapy (CRT) magnetic resonance imaging (MRI) tumour regression grading (TRG) system. SCC squamous cell carcinoma