Background and rationale
Methods/Design
Study design
Study objectives
Baseline | ||||||
---|---|---|---|---|---|---|
Follow-up | Diameter | 35 mm | 30 mm | 25 mm | 20 mm | 15 mm |
35 mm | 0 | |||||
30 mm | I° | 0 | ||||
25 mm | II° | I° | 0 | |||
20 mm | III° | II° | II° | 0 | ||
15 mm | IV° | IV° | III° | II° | 0 |
Sample size calculation
Statistical analysis
Participants/patient selection
- Female patient
- Histologically confirmed squamous anal cancer
- Indication for definitive or postoperative radiotherapy*
- ECOG 0–2
- Age > 18 years
- Written informed consent
- patient’s refusal or incapability of informed consent
- no vaginal dilation possible prior to radiation treatment start
- clinical evidence of tumor infiltration of the vagina or vulva
- prior pelvic irradiation (if direct field border or even overlap of radiation fields assumed)
- participation in another clinical trial which might influence the results of the DILANA trial
- pregnancy/nursing period or inadequate contraception in women with child bearing potential
Investigation schedule (Fig. 1)
Radiotherapy-planning
- Bladder: Whole organ including the bladder neck.
- Rectum: From the ano-rectal sphincter to the recto-sigmoid junction.
- Sigmoid: From the recto-sigmoid junction to the left iliac fossa.
- Bowel: Outer contour of bowel loops including the mesenterium.
- Femoral heads: Both femoral head and neck to the level of the trochanter minor.
- Vagina: whole vagina from the introitus to the cervix including the tampon and the surrounding soft tissue of the vaginal wall. The ventral and posterior half of the vaginal wall are contoured separately. A possible overlap of the PTV with the vagina (PTV_Vagina) will be documented separately. The anatomical vaginal reference points defined at the level of the Posterior-Inferior Border of Symphysis (PIBS) and ± 2 cm will be applied.
- Cauda equina: dural sac from the second lumbar vertebra to the sacrum.
Range | Organ at risk | Parameter | Constraint Optimal (tolerable) |
---|---|---|---|
1 | Bladder | Dmean | < 30 Gy (< 40 Gy) |
2 | Sigma | Dmax | < 50 Gy (< 57 Gy) |
3 | Colon | Dmax 200 cc | < 50 Gy (< 54 Gy) < 30 Gy |
4 | Cauda equina | Dmax | < 25 Gy (< 45 Gy) |
5 | Femoral heads | Dmean | < 30 Gy (< 35 Gy) |
6 | Vagina | Dmean | < 40 Gy |
Target volume definition
- GTV_LN: macroscopic lymph node metastases (short axis diameter > 1 cm [exept inguinal] and/or other morphological imaging signs of malignancy, ultrasound correlation can be used if necessary)
- CTV_BoostPT:
- if macroscopic primary tumor: GTVPT + 5–10 mm, complete anal canal, sphincter muscle
- in case of Rx/R1-situation: preoperative tumor extension + 5–10 mm, complete anal canal, sphincter muscle
- CTV_BoostLN: GTVLN + 3 mm
- CTV_LAD (lymphatic drainage):
- peri−/mesorectal, presacral, internal and extern iliacal, inguinal (may not be necessary in case of T1 cN0), ischiorectal fossa, perineal
- cranial border: promontory
- PTV_BoostPT: CTV_BoostPT + 5–10 mm
- PTV_BoostLN: CTV_BoostLN + 5–10 mm
- PTV_LAD: CTV_LAD + 5–10 mm
Monitoring during treatment/adverse events
Symptom | 1° | 2° | 3° | 4° | 5° |
---|---|---|---|---|---|
Proctitis – A disorder characterized by inflammation of the rectum. | Rectal discomfort, intervention not indicated | Symptomatic (e.g., rectal discomfort, passing blood or mucus); medical intervention indicated; limiting instrumental ADL | Severe symptoms; fecal urgency or stool incontinence; limiting self care ADL | Life-threatening consequences; urgent intervention indicated | Death |
Diarrhea – A disorder characterized by an increase in frequency and/or loose or watery bowel movements. | Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline | Increase of 4–6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental ADL | Increase of > = 7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL | Life-threatening consequences; urgent intervention indicated | Death |
Cystitis noninfective – A disorder characterized by inflammation of the bladder which is not caused by an infection of the urinary tract | Microscopic hematuria; minimal increase in frequency, urgency, dysuria, or nocturia; new onset of incontinence | Moderate hematuria; moderate increase in frequency, urgency, dysuria, nocturia or incontinence; urinary catheter placement or bladder irrigation indicated; limiting instrumental ADL | Gross hematuria; transfusion, IV medications, or hospitalization indicated; elective invasive intervention indicated | Life-threatening consequences; urgent invasive intervention indicated | Death |
Anal mucositis – A disorder characterized by ulceration or inflammation of the mucous membrane of the anus | Asymptomatic or mild symptoms; intervention not indicated | Symptomatic; medical intervention indicated; limiting instrumental ADL | Severe symptoms; limiting self care ADL | – | – |
Vaginal dryness – A disorder characterized by an uncomfortable feeling of itching and burning in the vagina | Mild vaginal dryness not interfering with sexual function | Moderate vaginal dryness interfering with sexual function or causing frequent discomfort | Severe vaginal dryness resulting in dyspareunia or severe discomfort | – | – |
Vaginal discharge – A disorder characterized by vaginal secretions | Mild vaginal discharge (greater than baseline for patient) | Moderate to heavy vaginal discharge; use of perineal pad or tampon indicated | – | – | – |
Vaginal inflammation - A disorder characterized by inflammation involving the vagina. Symptoms may include redness, edema, marked discomfort and an increase in vaginal discharge | Mild discomfort or pain, edema, or redness | Moderate discomfort or pain, edema, or redness; limiting instrumental ADL | Severe discomfort or pain, edema, or redness; limiting self care ADL; small areas of mucosal ulceration | Life-threatening consequences; widespread areas of mucosal ulceration; urgent intervention indicated | – |
Vaginal stricture – A disorder characterized by a narrowing of the vaginal canal | Asymptomatic; mild vaginal shortening or narrowing | Vaginal narrowing and/or shortening not interfering with physical examination | Vaginal narrowing and/or shortening interfering with the use of tampons, sexual activity or physical examination | – | Death |
Follow up
- update of medical history and documentation of the results of the latest imaging performed as part of the regular oncological follow-up
- assessment of symptoms and treatment toxicity according to the CTC AE version 5.0 criteria
- assessment of compliance regarding the regular use of the vaginal dilator
- assessment of quality of life assessed with the EORTC-QLQ30/−ANL27 questionnaires
- at 6 weeks and 12 months: measurement of the vaginal diameter using the vaginal dilator set