23. Anal Cancer - The GEC-ESTRO Handbook of Brachytherapy

Anal Cancer

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THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part II Clinical Practice Version 1 - 01/03/2023

13. ADVERSE EVENTS

Multimodal imaging assessment combining conventional imaging (CT and/or MRI), and functional imaging (PET-scan), is recommended for the detection of progression and recurrence (figure 10) [17,46]. Furthermore, a post-therapy PET scan showing resolution of metabolic activity has been reported to be highly associated with improved progression-free survival. A post-treatment PET scan demonstrating resolution of metabolic activity performed 3months compared with 1 month after completion of treatment may yield higher sensitivity (100% vs. 66%) and specificity (97.4% vs. 92.5%) with respect to predicting outcomes [46]. It should be noted that tumour regression can be observed up to 6 months after brachytherapy. Overall results A recent meta-analysis [24] of 10 series, including 1130 patients between 1970 and 2014 with a median follow-up ranging from 29 to 76 months, gives the most complete results for IBT in anal canal tumours. Overall, the 5-year local control (LC) was 78.8%, the 5-year colostomy-free survival (CFS) was 76.1% and the 5-year overall survival (OS) was 69.4%. Table 3 details the different published series on IBT boost. Stage T3-4 and poor responders after concurrent chemoradiation (less than 50%of tumour reduction) are overall negative prognostic factors, while node-negative status at diagnosis and good response to concurrent chemoradiation are positive prognostic factors. Comparison between EBRT and IBT boost No comparative trial exists to rigorously compare between EBRT and IBT boost. The CORS-03 study reported that boost type was one of the prognostic factors for 5-year LC (IBT: 88% vs. EBRT: 67%) and CFS (IBT: 71% vs. EBRT: 56%). In addition, surgery (for progression or complications) was needed in 26% of EBRT boost patients but only in 8% of IBT boost patients [25]. Other studies [37,47] also reported superior 5-year OS and DFS for IBT. However, some authors found no significant impact of boost-type for their cohort [30,48,49] Comparison between dose rates Comparative studies are also lacking to properly compare between the different IBT modalities (LDR, PDR or HDR). Indirect comparisons between retrospective series seem to indicate that LDR, PDR and HDR offer similar local control rates, and reported rates of toxicity tend to compare favorably for the HDR approach [1,24]. More precisely, after HDR IBT the 5-year LC ranges from 80-90%, OC from 70-80% and CFS from 75-90% (see table 3). In Doniec et al. [35], sphincter function was completely preserved in 80% of HDR patients. Falk et al. [42] reported only grade 1 acute toxicities (genitourinary: 37%, gastrointestinal: 41%, cutaneous: 4%). 12. RESULTS

Acute toxicity Most patients experience acute local toxicity during radiation. Systematic reviews [1,24] report grade 1-2 dermato-mucositis ranging from 30-60% and proctitis from 10-30%. Grade 3 and 4 acute toxicities were also reported, ranging from 10-30%, often leading to unplanned treatment breaks and longer OTT. Oehler-J. et al. [48] reported higher grade 3-4 toxicity with EBRT compared to IBT boost (43% vs. 15%), particularly for severe cutaneous toxicity (23% vs. 8%). Severe diarrhoea occurred in 6% in both subgroups. Gryc et al. [38] showed no disparity between EBRT and IBT boost. Principal acute toxicities are: - Gastrointestinal toxicities: acute proctitis, intermittent anal- rectal bleeding, diarrhoea - Genitourinary toxicities: frequent urination, dyspareunia, vulvo-vaginal symptoms - Acute dermatitis Late toxicity Most common late toxicity is sphincter dysfunction with grade 1-2 (25%), grade 3 (10%) and grade 4 (4%) incontinence [1]. Other gastrointestinal late toxicities are: - Anal fibrosis: grade 1-2 fibrosis (0-25%) and grade 3 stricture (<5%). Complete obstruction is extremely rare - Intermittent anorectal bleeding: grade 1-2 is frequent (15- 70%), but grade 3-4 is rare (<2%) - Necrosis is uncommon: grade 2 occurs in <10% and grade 3-4 in <5% - Other toxicities include proctitis (0-26%), chronic abdominal pain (0-15%), skin toxicity (0-10%) and fistulae (0-1%) Grade 3 late genitourinary toxicities occur in less than 5% of cases [24] and include haematuria, urinary incontinence, urinary frequency, dysuria, and vaginal strictures. Permanent colostomy related to toxicity is typically reported for less than 5% of patients, with 3.7%median rate [24].The most frequent toxicities leading to colostomy were radio-necrosis, followed by severe incontinence, bleeding, pain and fistula. Lestrade et al. [32] reported a significant correlation between total dose and the risk of late severe toxicities (3% for doses <63Gy, 10% for >63Gy). Series mostly report less late toxicity in cases of IBT boost than in cases of EBRT boost. For instance, in the CORS 3 study, there was a rate of abdominoperineal resection due to toxicity of 5% after EBRT and of 3% after IBT boost [25]. Arcelli et al. [37], Gryc et al. [38] and Oehler-J. and al. [48] found no significant difference between EBRT and IBT boost for severe late toxicity and overall quality-of-life. The rates of severe late toxicity are significantly correlated to the total equivalent dose and the volume treated. When two plane techniques were used historically there was also a higher rate of severe toxicity compared to the one plane technique [50].