Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer

Jelena Lukovic; Ali Hosni; Amy Liu; Jasmine Chen; Tony Tadic; Tirth Patel; Kecheng Li; Kathy Han; Patricia Lindsay; Tim Craig; James Brierley; Aisling Barry; Rebecca Wong; Jolie Ringash; Laura A Dawson; John J Kim

doi:10.1016/j.radonc.2022.11.018

Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer

Radiother Oncol. 2023 Jan:178:109429. doi: 10.1016/j.radonc.2022.11.018. Epub 2022 Nov 28.

Authors

Affiliations

¹ Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Electronic address: Jelena.lukovic@rmp.uhn.ca.
² Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
³ Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Electronic address: zhihuiamy.liu@uhnresearch.ca.
⁴ Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.
⁵ Techna Institute, Toronto, ON, Canada.
⁶ Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

PMID: 36455685
DOI: 10.1016/j.radonc.2022.11.018

Abstract

Background: This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy.

Materials and methods: Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 1&5). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea).

Results: In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder D_0.5cc; G2 + inguino-genital skin toxicity and anterior skin V35; G2 + perianal skin toxicity and posterior skin V15; G2 + anemia and lower pelvis bone V45. D0.5 cc was significantly predictive of late toxicity (G2 + anal dysfunction, intestinal toxicity, and inguino-genital/perianal dermatitis). Maximum skin toxicity grade was significantly correlated with the requirement for a treatment break.

Conclusion: Statistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

Keywords: Anal cancer; Dosimetry; Radiation therapy.

Publication types

Observational Study

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Anus Neoplasms* / drug therapy
Chemoradiotherapy / adverse effects
Chemoradiotherapy / methods
Dermatitis* / drug therapy
Dermatitis* / etiology
Diarrhea / etiology
Fluorouracil / adverse effects
Humans
Mitomycin / adverse effects
Radiotherapy, Intensity-Modulated* / adverse effects
Radiotherapy, Intensity-Modulated* / methods

Substances

Fluorouracil
Mitomycin