Study of SIB-IMRT in Combination With 5-FU and Mitomycin-C Among Patients With Locally Advanced Anal Canal Cancer: Efficacy, Safety and Quality of Life

• 5Fluorouracile and Mitomycin-C (Drug): All the patients will receive radiochemotherapy with two cycles of 5FU (1,000 mg/m²/d with 96-h infusion, days 1-5 and 29-33 of SIB-IMRT) and Mitomycin-C (10 mg/m², days 1 and 29).
• Simultaneously integrated boost of intensity modulated radiation therapy (SIB-IMRT) by tomotherapy (Radiation): SIB-IMRT schedule of 61.2 Gy/1.7 Gy to the primary tumor, 57.60 Gy / 1.6 Gy to involved nodes, and 54 / 1.5 Gy to elective pelvic lymph nodes.

Primary outcomes

• Efficacy: The 3-month Locoregional Control Rate [3 months after the end of radiotherapy]: The 3-month locoregional control rate after the end of IMRT by helical tomotherapy defined by the proportion of patients alive with no local disease progression 3 months after the end of radiotherapy
• Tolerance Profile: Proportion of Patients With no Significant Toxicities Responsible for Irradiation Breaks [Until 11 weeks after treatment start]: Tolerance profile: Proportion of patients with no significant (grade ≥3 according to NCI CTCAE v4.03) toxicities responsible for irradiation breaks

Secondary outcomes

• Quality of Life Measured by the EORTC QLQ-C30 (Version 3.0) [6 months after treatment start]: The EORTC QLQ-C30 is a cancer-specific health-related quality of life questionnaire comprising 30 items. It assesses five functional domains (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, pain, and nausea/vomiting), a global health status/quality of life scale, and several single-item symptom measures. Scores are linearly transformed to a 0-100 scale; higher functional and global health scores indicate better functioning/quality of life, whereas higher symptom scores indicate greater symptom burden.
• The Acute and Late Toxicities Assessed According to NCI CTCAE v4.03 [From treatment start to 24 months after the end of radiotherapy]: Acute toxicity is defined as toxicity observed within 3 months after treatment initiation. Late toxicity is defined as toxicity observed 3 months after treatment initiation. Here we described the number of patients who observed acute and late toxicities. Details will be given in adverse events description.
• The 6- and 12-month Locoregional Control Rates Defined by the Proportion of Patients With no Local Disease Progression at 6 and 12 Months After the End of Radiotherapy [at 6 and 12 months after the end of radiotherapy]
• Duration of Response Defined by the Time Elapsed From First Objective Response to Progression or Death From Any Cause [From months 3 to progression]
• Quality of Life Measured by the Additional Colorectal Module QLQ-CR 29 [6 months after treatment start]: The EORTC QLQ-CR29 is a colorectal cancer-specific quality of life module designed to complement the QLQ-C30. It assesses disease- and treatment-related symptoms and functional issues, including urinary frequency, blood and mucus in stool, stool frequency, body image, anxiety, sexual function, and other gastrointestinal and treatment-related symptoms. Scores are linearly transformed to a 0-100 scale; higher functional scores indicate better functioning, whereas higher symptom scores indicate greater symptom burden.
• Quality of Life Measured by the Vaizey Incontinence Scale [6 months after treatment start]: Vaizey Score (St. Mark's Incontinence Score): a validated instrument used to assess anal sphincter function and the severity of fecal incontinence. The scale evaluates the frequency of incontinence to gas, liquid, and solid stool, the need to wear pads, use of constipating medication, and lifestyle alterations. Scores range from 0 to 24, with higher scores indicating worse continence and greater impairment of sphincter function.
• The Acute Toxicities Assessed According the SOMA/LENT Scale [At 3 months after treatment initiation]: The Subjective SOMA/LENT (Late Effects on Normal Tissues - Subjective, Objective, Management, and Analytic) scale assesses patient-reported late radiation toxicity across multiple symptom domains. Each symptom item (e.g., stool frequency, urinary frequency, vaginal dryness, dyspareunia) is scored separately on a 5-point ordinal scale ranging from 0 to 4, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms, and 4 = very severe or disabling symptoms. Higher scores indicate worse late radiation-related toxicity. No overall total score was calculated; each symptom domain is reported separately.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* WHO performance status ≤ 2
* Age > 18 years
* Epidermoid anal canal carcinoma histologically proven, locally advanced with an indication of radiation of pelvic and inguinal nodes concomitantly to chemotherapy
* The T corresponds to the larger dimension of tumor at the rectal examination and the N is assessed by imaging pelvic MRI-imaging, CT-scan, optionally PET-CT). Eligible tumors are: T2 more than 4 cm N0-N3, T2-T4 N1-N3 or usN1, T3-T4 N0, M0 according to the 6th edition of the American Joint Committee on cancer staging manual.
* Laboratory data obtained ≤ 14 days prior to registration on study, with adequate bone marrow, hepatic and renal function defined as follows: hemoglobinemia, neutrophil, platelet counts, bilirubin and creatinin level
* Informed consent form

Exclusion Criteria:

* Previous invasive cancer within 5 years except basocellular cancer and in situ cervical cancer
* Tumors with predominant skin involvement
* Presence of metastases
* History of pelvic irradiation
* Contraindication to radiotherapy or chemotherapy
* Known HIV positive patients

Participant flow

Outcome results

• Efficacy: The 3-month Locoregional Control Rate (Primary), Count of participants, Participants: Concomitant Chemotherapy and Radiotherapy 63
• Tolerance Profile: Proportion of Patients With no Significant Toxicities Responsible for Irradiation Breaks (Primary), Count of participants, Participants: Concomitant Chemotherapy and Radiotherapy 60
• Quality of Life Measured by the EORTC QLQ-C30 (Version 3.0) (Secondary), Mean, units on a scale: Concomitant Chemotherapy and Radiotherapy 82.6 +/- 21.8
• The Acute and Late Toxicities Assessed According to NCI CTCAE v4.03 (Secondary), Count of participants, Participants: Concomitant Chemotherapy and Radiotherapy 70
• The 6- and 12-month Locoregional Control Rates Defined by the Proportion of Patients With no Local Disease Progression at 6 and 12 Months After the End of Radiotherapy (Secondary), Count of participants, Participants: Concomitant Chemotherapy and Radiotherapy 61
• Duration of Response Defined by the Time Elapsed From First Objective Response to Progression or Death From Any Cause (Secondary), Mean, month: Concomitant Chemotherapy and Radiotherapy 41.3 +/- 17.2
• Quality of Life Measured by the Additional Colorectal Module QLQ-CR 29 (Secondary), Mean, units on a scale: Concomitant Chemotherapy and Radiotherapy 81 +/- 24.9
• Quality of Life Measured by the Vaizey Incontinence Scale (Secondary), Mean, units on a scale: Concomitant Chemotherapy and Radiotherapy 7 +/- 6.9
• The Acute Toxicities Assessed According the SOMA/LENT Scale (Secondary), Mean, units on a scale: Concomitant Chemotherapy and Radiotherapy 1.05 +/- 0.87

Adverse events

Time frame: From treatment start up to 24 months

Serious adverse events by term

Other adverse events by term

95 more terms not shown.

• Study Protocol and Statistical Analysis Plan (PDF, 2024-12-02)

• Carmen FLORESCU, MD, Principal investigator, Centre François Baclesse