Montag, 19. April 2021
Navigation öffnen
Anzeige:
Lonsurf
 
JOURNAL ONKOLOGIE – STUDIE
SENNAN

A Prospective Study Comparing Three Injection Sites to Detect Sentinel Lymph Nodes in Endometrial Cancer

Rekrutierend

NCT-Nummer:
NCT04577950

Studienbeginn:
Januar 2021

Letztes Update:
27.01.2021

Wirkstoff:
-

Indikation (Clinical Trials):
Endometrial Neoplasms

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Centre Hospitalier Universitaire Vaudois

Collaborator:
-

Studienleiter

Patrice Mathevet, MD - PhD
Principal Investigator
Centre Hospitalier Universitaire Vaudois

Kontakt

Patrice Mathevet, MD- PhD
Kontakt:
Phone: +41213146727
Phone (ext.): +41
E-Mail: patrice.mathevet@chuv.ch
» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Studien-Informationen

Detailed Description:

Worldwide, in 2012, 527'600 women were diagnosed with uterine cancer. It is the most common

gynecologic malignancy in developed countries. In developing countries, it is the second most

common, just behind cervical cancer. Adenocarcinoma of the endometrium is the most common

histologic site and type of uterine cancer. Endometrial cancer is the fifth most frequent

cancer in women in Switzerland. The incidence rose up to 5.9% in 2015. This tumor affects

mainly older women, at 63 years on average. The majority of women are diagnosed at an early

stage: confined to primary site for 67%, spread to regional organs and lymph nodes for 21%

and with distant metastasis for 8%. Seventy-five to 90% of the patients are alerted by

abnormal uterine bleeding very quickly, which allows a quick management of care and a high

survival rate.

Besides age, one of the main risk factor of developing an endometrial carcinoma is obesity.

In fact, obese women have higher risk to have an endometrial cancer, but also at a younger

age than the average and finally they have an increased risk of death due to this particular

cancer. Although the investigators are not sure of the reasons, it may be linked to the

co-morbidities that go with obesity like diabetes or hypertension.

The treatment of endometrial cancer in most women is surgery involving a total hysterectomy

and a bilateral salpingo-oophorectomy with or without a lymph node dissection. For patients

with early stage endometrial cancer, there is a disagreement among cancer centers regarding

lymph nodes dissection, because randomized controlled trials and a meta-analysis have shown

no clear evidence on overall or recurrence-free survival and a higher incidence on early and

late complications in relation with pelvic lymph node dissection. A systematic lymph node

dissection consists of removing all the nodes within a nodal drainage basin irrespective of

size. The problem with that technique is that dissection proves to be very difficult in obese

patient and includes a risk to damage blood vessels or nerves.Moreover, lymph node dissection

is associated with a higher morbidity, longer operating time, more frequent blood loss and

finally symptomatic lymphedema and seroma. Indeed, the risk of leg lymphedema due to a node

dissection is often under-reported, with rates going from 5% to 38%.

That is why, sentinel lymph node biopsy (SLNB) seems to many authors to be a good alternative

to lymph node dissection. The tumor's spread is assessed in lymph nodes with a reduced

morbidity. In fact, lymphadenectomy and its dangerous complications, like lymphedema, could

be avoided in the vast majority of cases. In cutaneous melanoma or in breast's cancer, this

technique is already widely used throughout the world. A sentinel node is the first node

involved in the movement of the tumor from the primary cancer to the lymph nodes. When tumor

cells spread to lymphatic network, they arrive in the first place in that sentinel node. If

it contains no metastasis, then nodes, on the lymph path below, will not be affected either.

Not only SLNB in endometrial cancer is associated with a reduction in morbidity compared to

lymph node dissection, but with it, a personalized treatment can be developed. Indeed, a

histological analysis of these sentinel lymph-nodes (SLNs) leads to ultrastadification:

cancers are graded depending on the presence and the size of metastasis in lymph nodes.

Adjuvant treatments, such as radiotherapy or chemotherapy, can be suggested following these

data and a better management of endometrial cancer is possible. Now, when lymph-node status

is still unknown, indication for adjuvant therapies are based on pathological features of

surgical specimens of the tumor, exposing some patients to either overtreatment or

undertreatment.

In fact, five-year disease free survival in stage I patients with positive SLNs is 54%,

whereas survival with negative SLNs is up to 90%.Therefore, SLN is one of the most important

prognostic factors in endometrial cancer.

Primary objective of SENNAN study: The study seeks primarily to compare the location of

uterine SLNs depending on the injection sites of the tracers: whether in endometrium, in

uterine isthmus or in the cervix.

Secondary objectives are:

1. A comparison of the sensitivity of the tracers to detect SLNs

2. A description of the incidence of adverse events

3. An evaluation of additional time required to identify SLNs with or without lymph node

dissection.

4. A description of morbidity directly induced by the search of SLNs

5. A calculation of negative predictive value of the different markers and their

associations

6. A correlation between the anatomical locations of the SLNs and ultrastadification of

SLNs.

7. An evaluation of the data of the lymphatic drainage, depending on tumor location in the

uterus.

8. An evaluation of the data of the lymphatic drainage, depending on histological grade of

the tumor.

9. An analysis of cases wherein change in the treatment have been made related to results

of detection of SLNs.

Procedure:

The patients will have the day before the surgery an identification of the sentinel nodes

with radiocolloid (Nanocoll®). The marker at a radioactivity of 80 MBq will be injected in

four points in the cervix, 0.2 ml of 20 millibecquerel each. A CTscintigraphy will be

performed three or four hours after the injection. The day of the surgery, the patients will

undergo a general anaesthesia and then under general anaesthesia, the first step of the

surgery will be to do the injection of the other two markers :

- ICG® will be injected through hysteroscopic guidance apart of the tumoral lesions at 4

points of injections. The volume of injected ICG will be 0.5 ml at each injection at the

concentration of 5 mg/ml. A total of 2 ml (10mg) of ICG will be used.

- Patent blue® will be diluted with 2 ml of physiologic serum. Then it will be injected

through the cervix along the uterus isthmus at the 3 o'clock and 9 o'clock level. 2 ml

will be injected on each side.

Then the patients will have a laparoscopic surgical approach with identification of the

sentinel nodes in the pelvic and lower abdomen areas. After identification of all the

sentinel nodes : blue and / or radioactive and / or fluorescent nodes, the patients will have

a total hysterectomy with bilateral oophorectomy and salpingectomy. The surgical technique

for this procedure is the same as the one usually performed for this kind of lesions.

The major benefit of looking for SLNs in endometrial cancer is that lymphadenectomy can be

avoided for patients who have already comorbidities. Indeed, endometrial cancer is found in

aged women and obese women are also more affected. Lymphadenectomy is a heavy procedure with

a risk of lymphedema. That is why the technique of SLNs offers a good alternative with lesser

surgical risks.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Informed Consent as documented by signature

- Early endometrial cancers (of International Federation of Gynecology and Obstetrics

stage IA-IB), whatever histological grade and type

- Primary surgical treatment with hysterectomy

- No metastasis, no other cancers, no recurrency of cancers

- No signs of lymph nodes metastasis on the preoperative workup (MRI +/- positron

emission computed tomography)

- No contraindication to laparoscopic procedures.

- Women of > 18 years

Exclusion Criteria:

- Known severe allergies (antecedents of Quincke oedema, anaphylactic shock,…) and a

history of allergy to iodides

- Contraindications to the injected products because of known hypersensitivity or

allergy to ICG of blue dye

- Antecedent of pelvic lymph nodes surgery

- Previous lymphadenectomy or surgery that could change the uterine lymphatic drainage

(conisation or myomectomy)

- Other diagnosed cancer during treatment or care

- Stage II and above (tumor invading cervix stroma) including those after a neo-adjuvant

treatment

- Suspicion of lymph nodes metastasis at preoperative workup

- Medical or uterine conservative treatment

- Patient, who does not understand, speak or write in French

- Drugs that can interfere with ICG : anti convulsants - bisulphite compounds -

haloperidol - heroin - pethidine [meperidine] - methamizole - methadone - morphine -

nitrofurantoin - opium alkaloids - phenobarbitone- phenylbutazone - cyclopropane -

probenecid - rifamycin - sodium bisulphite (mostly combined with heparin)

- Radioactive iodine uptake performed less than one week following the use of ICG.

- Hypersensitivity to Nanocoll, to any of the excipients (Stannous chloride, dihydrate

Glucose, anhydrous Poloxamer 238 Sodium phosphate, dibasic, anhydrous Sodium phytate,

anhydrous) or to any of the components of the labelled radiopharmaceutical.

- A history of hypersensitivity to products containing human albumin

- Hypersensitivity to dyes made of triphenylmethane

- Lymphostasis

Studien-Rationale

Primary outcome:

1. Lymphatic route of endometrial cancer dissemination (Time Frame - 1 month):
Comparing the per-operative anatomical locations of uterine SLNs depending on the 3 different injection sites of the tracers: whether in endometrium, in uterine isthmus or in the cervix.



Secondary outcome:

1. Sensibility/sensitivity of the tracers (Time Frame - 1 month):
A comparison of the sensibility/sensitivity of the tracers to detect SLNs

2. Adverse events (Time Frame - 1 month):
A description of the incidence of adverse events

3. Additional time required to identify SLNs (Time Frame - 1 month):
An evaluation of additional time required to identify SLNs with or without lymph node dissection.

4. Morbidity directly induced by the search of SLNs (Time Frame - 1 month):
A description of morbidity grades (following the NCI CTCAE classification) directly induced by the search of SLNs

5. Negative predictive value of the different markers (Time Frame - 1 month):
A calculation of negative predictive value of the different markers and their associations

6. Correlation between the per-operative anatomical locations of the SLNs and ultrastadification of SLNs. (Time Frame - 1 month):
A correlation between the per-operative anatomical locations of the SLNs and the results of ultrastadification of these SLNs.

7. Comparison between the results of lymphatic drainage and location of the tumor. (Time Frame - 1 month):
An evaluation of the anatomical location of the SLNs depending on uterine location of the tumor. The anatomical locations would be divided in 3 different sites: pelvic, para-aortic and parametrial. The location of the tumor would be divided in 3 sites: uterine horns, uterine fundus, uterine walls.

8. Comparison between the results of lymphatic drainage and grade of the tumor. (Time Frame - 1 month):
An evaluation of the anatomical location of the SLNs depending on grade of the tumor. The anatomical locations would be divided in 3 different sites: pelvic, para-aortic and parametrial. The location of the tumor would be divided in 3 grades: 1, 2 and 3

9. Cases with change in treatment in relation with SLNs detection and histology. (Time Frame - 1 month):
Description of cases wherein change in the treatment have been made related to results of different anatomical locations and pathological (including ultrastadification) results of SLNs.

Geprüfte Regime

  • Lymphatic drainage of endometrial cancer:
    Nanocoll® is injected a day before surgery in the cervix at four points. A lymphoscintigraphy is performed 2 or 3 hours afterward. At the beginning of the surgery, the operative field already in place and before the beginning of laparoscopic, 2ml (10mg) of ICG, distributed in four points around the tumor, is injected under the endometrium intra-myometrial under endoscopic control. As ICG spreads slower than blue dye, ICG is always injected first. Then, Bleu Patenté® is injected at two sites in the uterine isthmus, opposite of the uterine arteries. The risk of false negative results, because a tracer migrated too quickly, is reduced when the injection takes place when patients are already anesthetized.

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren
Krebstherapien können Herz und Gefäße schädigen: Wie schützt man Patienten?
Krebstherapien+k%C3%B6nnen+Herz+und+Gef%C3%A4%C3%9Fe+sch%C3%A4digen%3A+Wie+sch%C3%BCtzt+man+Patienten%3F
©freshidea / Fotolia.de

Die Therapie von Krebserkrankungen hat in den letzten Jahren große Fortschritte gemacht. Verbesserte Operationsmethoden, eine präzisere Strahlenbehandlung und neue Medikamente konnten die Überlebenschancen der Patienten deutlich verbessern. Doch der Fortschritt hat seinen Preis: „Viele Krebstherapien können Herz und Kreislauf schädigen – auch die modernen, zielsicherer an Krebszellen ansetzenden...