"NV16-31643A" Dotaz Zobrazit nápovědu
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Standard treatment in early stages cervical cancer includes systematic pelvic lymphadenectomy which is associated with significantly increased risk of postoperative morbidity. Sentinel lymph node (SLN) biopsy in the management of cervical cancer has been extensively studied, so a detection technique is well standardized, and very low false negative rate in staging of pelvic lymph nodes has been well documented. However, SLN biopsy is still not used in current clinical practice since a prospective study on oncological outcome has not been performed yet. It is the aim of this project to conduct a multicenter randomized prospective trial comparing SLN biopsy versus systematic pelvic lymphadenectomy. The protocol entails all requirements for phase III clinical trial including randomization, central quality assurance and clinical monitoring. The trial has a realistic potential to reach a calculated number of cases required for the survival assessment and thus brings a level A evidence data which are essential for changing of the international guidelines.
Systematická pánevní lymfadenektomie je standardní součástí léčby časných stádií karcinomu děložního hrdla. Tento výkon významně zvyšuje riziko pooperační morbidity. Biopsie sentinelové uzliny (SLN) byla v léčbě časných stádií karcinomu děložního hrdla intenzivně studována. Metodika detekce SLN je dobře standardizována a nízká falešná negativita ve stagingu pánevních lymfatických uzlin je dostatečně doložena. Přesto biopsie SLN není využívána v klinické praxi, protože dosud nebyla provedena prospektivní studie s cílem hodnotit přežití pacientek. Hlavním cílem projektu je uspořádat multicentrickou randomizovanou prospektivní studii srovnávající provedení pouze odběru SLN versus systematické pánevní lymfadenektomie. Protokol studie splňuje kritéria pro klinickou studii fáze III, včetně randomizace, centrálního ověřování kvality a klinického monitoringu. Projekt má reálný potenciál dosáhnout počtu pacientek nutného k analýze přežití a tedy k získání výsledků nejvyšší evidence, které povedou ke změně mezinárodních doporučení.
- MeSH
- analýza přežití MeSH
- biopsie sentinelové lymfatické uzliny metody MeSH
- lidé MeSH
- lymfadenektomie metody MeSH
- morbidita MeSH
- nádory děložního čípku terapie MeSH
- prospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- onkologie
- gynekologie a porodnictví
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
BACKGROUND: The management of patients with intraoperative detection of lymph node involvement remains controversial. The most significant aspect is the decision regarding the completion of the cervical procedure, such as hysterectomy, radical hysterectomy, or a fertility sparing procedure. PRIMARY OBJECTIVE: The primary objective of the ABandoning RAd hyst in cerviX cancer (ABRAX) trial is to determine whether the completion of the cervical procedure (ie, radical hysterectomy) improves oncological outcome in patients with intraoperatively detected lymph node involvement before they are referred for definitive chemoradiation. STUDY HYPOTHESIS: We hypothesize that, in patients with intraoperative lymph node involvement, completion of radical hysterectomy or other cervical procedure does not improve the oncological outcome of definitive chemoradiation. TRIAL DESIGN: The ABRAX trial is a multicenter, retrospective, cohort study. Patients with negative lymph nodes in clinical staging, in whom lymph node involvement is detected intraoperatively, are included. Completion or abandonment of the planned cervical procedure stratifies the cohort into two subgroups in which oncological outcome and morbidity will be compared. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients with early stage (pT1a-pT2b) cervical cancer, who did not have positive lymph nodes on preoperative imaging, who were scheduled for primary surgical treatment, and in whom metastatic involvement of pelvic lymph node was found during surgery either as a grossly (macroscopically) involved or on intraoperative pathology assessment will be enrolled. Patients can be included irrespective of surgical approach (minimal invasive surgery or laparotomy) and type of cervical procedure performed (hysterectomy, radical hysterectomy, or a fertility sparing procedure). PRIMARY ENDPOINT: The primary endpoint of this retrospective study is a progression free survival in two subgroups with abandoned or completed cervical procedure followed by definitive chemoradiation in both groups. SAMPLE SIZE: The assumed sample size is 718 patients (in total for both groups). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Estimated end of data collection: December 2019; estimated date of presenting results: Q2/3 2020. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04037124.
- MeSH
- adjuvantní chemoradioterapie MeSH
- doba přežití bez progrese choroby MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- lymfatické uzliny patologie MeSH
- nádory děložního čípku farmakoterapie patologie radioterapie chirurgie MeSH
- peroperační péče metody MeSH
- retrospektivní studie MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
The data on the prognostic significance of low volume metastases in lymph nodes (LN) are inconsistent. The aim of this study was to retrospectively analyze the outcome of a large group of patients treated with sentinel lymph node (SLN) biopsy at a single referral center. Patients with cervical cancer, stage T1a-T2b, common tumor types, negative LN on preoperative staging, treated by primary surgery between 01/2007 and 12/2016, with at least unilateral SLN detection were included. Patients with abandoned radical surgery due to intraoperative SLN positivity detected by frozen section were excluded. All SLNs were postoperatively processed by an intensive protocol for pathological ultrastaging. Altogether, 226 patients were analyzed. Positive LN were detected in 38 (17%) cases; macrometastases (MAC), micrometastases (MIC), isolated tumor cells (ITC) in 14, 16, and 8 patients. With the median follow-up of 65 months, 22 recurrences occurred. Disease-free survival (DFS) reached 90% in the whole group, 93% in LN-negative cases, 89% in cases with MAC, 69% with MIC, and 87% with ITC. The presence of MIC in SLN was associated with significantly decreased DFS and OS. Patients with MIC and MAC should be managed similarly, and SLN ultrastaging should become an integral part of the management of patients with early-stage cervical cancer.
- Publikační typ
- časopisecké články MeSH
The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review.
- Publikační typ
- časopisecké články MeSH
CONTEXT.—: Ultrastaging of sentinel lymph nodes (SLNs) is a crucial aspect in the approach to SLN processing. No consensual protocol for pathologic ultrastaging has been approved by international societies to date. OBJECTIVE.—: To provide a review of the ultrastaging protocol and all its aspects related to the processing of SLNs in patients with cervical cancer. DATA SOURCES.—: In total, 127 publications reporting data from 9085 cases were identified in the literature. In 24% of studies, the information about SLN processing is entirely missing. No ultrastaging protocol was used in 7% of publications. When described, the differences in all aspects of SLN processing among the studies and institutions are substantial. This includes grossing of the SLN, which is not completely sliced and processed in almost 20% of studies. The reported protocols varied in all aspects of SLN processing, including the thickness of slices (range, 1-5 mm), the number of levels (range, 0-cut out until no tissue left), distance between the levels (range, 40-1000 μm), and number of sections per level (range, 1-5). CONCLUSIONS.—: We found substantial differences in protocols used for SLN pathologic ultrastaging, which can impact sensitivity for detection of micrometastases and even small macrometastases. Since the involvement of pelvic lymph nodes is the most important negative prognostic factor, such profound discrepancies influence the referral of patients to adjuvant radiotherapy and could potentially cause treatment failure. It is urgent that international societies agree on a consensual protocol before SLN biopsy without pelvic lymphadenectomy is introduced into routine clinical practice.
Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stages cervical cancer instead of systematic pelvic lymph node dissection (PLND). The aim of this article is to give a critical overview of key aspects related to this concept, such as a necessity for reliable detection of micrometastases (MIC) in SLN and the requirements for SLN pathologic ultrastaging, low accuracy of intraoperative detection of SLN involvement, and still a limited evidence of oncological safety of the replacement of PLND by SLN biopsy only in ≥IB1 tumours due to unknown risk of MIC in non-SLN pelvic lymph nodes in patients with negative SLN, and absence of any prospective evidence.
OBJECTIVE: Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stage cervical cancer. It appears in guidelines as an alternative option to systematic pelvic lymphadenectomy. The evidence about safety is, however, based mostly on retrospective studies, in which SLN was combined with systematic lymphadenectomy. MATERIALS AND METHODS: SENTIX is a prospective multicenter trial aiming to prove that less-radical surgery with SLN is non-inferior to treatment with systematic pelvic lymphadenectomy. The primary end point is recurrence rate; the secondary end point is the prevalence of lower-leg lymphedema and symptomatic pelvic lymphocele. The reference recurrence rate was set up conservatively at 7% at 24 months after treatment. With a sample size of 300 patients treated per protocol, the trial is powered to detect a non-inferiority margin of 5% (90% power, p = 0.05) for recurrence rate, 30% reduction in the prevalence of symptomatic lymphocele or lower-leg lymphedema, with reference rates of 30% and 6% at 12 months (p = 0.025, Bonferroni correction). The patients eligible for SENTIX have stage IA1/LVSI+, IA2, IB1 (<2 cm for fertility sparing), with negative LN on pre-operative imaging. Intra-operatively, patients are excluded when there is a failure to detect SLN on both sides of the pelvis in cases of more advanced cancer (stage >IB1), or a positive intra-operative SLN assessment. The quality of SLN pathology evaluation will be assessed by central review. Three interim safety analyses are pre-planned when 30, 60, 150 patients complete 12 months' follow-up. CONCLUSIONS: The first patient was enrolled into the study in June 2016 and, by June 2018, 340 patients had been enrolled. The first analysis of secondary outcomes should be available in 2019 and the oncological outcome of 300 patients at the end of 2021. The trial is registered as a CEEGOG trial (CEEGOG CX-01), ENGOT trial (ENGOT-Cx 2), and at the ClinicalTrials.gov database (NCT02494063).
- MeSH
- adenokarcinom patologie chirurgie MeSH
- biopsie sentinelové lymfatické uzliny mortalita MeSH
- dospělí MeSH
- hysterektomie mortalita MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru diagnóza epidemiologie MeSH
- lymfadenektomie mortalita MeSH
- mezinárodní agentury MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory děložního čípku patologie chirurgie MeSH
- následné studie MeSH
- prospektivní studie MeSH
- senioři MeSH
- sentinelová uzlina patologie chirurgie MeSH
- spinocelulární karcinom patologie chirurgie MeSH
- staging nádorů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The role of adjuvant radiotherapy for lymph node-negative stage IB patients with tumor-related negative prognostic factors is not uniformly accepted. It is advocated based on the GOG 92 trial, which was initiated in 1989. The aim of the current study is to report the oncological outcome of "intermediate risk" patients treated by tailored surgery without adjuvant radiotherapy. Data from two institutions that refer these patients for adjuvant radiotherapy served as a control group. METHODS: Included were patients with stage IB cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, who had negative pelvic lymph nodes but a combination of negative prognostic factors adopted from the GOG 92 trial. Data were obtained from prospectively collected databases of three institutions. Radical surgery was a single-treatment modality in one of them and in the remaining two institutes it was followed by adjuvant chemoradiation. RESULTS: In 127 patients who received only radical surgery, with a median follow-up of 6.1 years, the local recurrence rate was 1.6% (2 cases), and total recurrence was 6.3% (8 cases). Disease-specific survival at 5 years was 95.7% (91.9%; 99.4%) and 91% (83.7%; 98.3%) at 10 years. The only significant factor for disease-specific survival was tumor size ≥4 cm (P = 0.032). The recurrence rate, local control or overall survival did not differ from the control group. Adjuvant radiotherapy was not a significant prognostic factor within the whole cohort. CONCLUSIONS: An excellent oncological outcome, especially local control, can be achieved by both radical surgery or combined treatment in stage IB lymph node-negative cervical cancer patients with negative prognostic factors. The substantially better outcome than in the GOG 92 trial can be attributed to more accurate pre-operative and pathological staging and an improvement in surgical techniques.
- MeSH
- adjuvantní radioterapie metody MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické uzliny patologie MeSH
- nádory děložního čípku patologie chirurgie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
OBJECTIVES: The aim of this study was to assess the detection rate, false-negative rate and sensitivity of SLN in LN staging in tumors over 2cm on a large cohort of patients. METHODS: Data from patients with stages pT1a - pT2 cervical cancer who underwent surgical treatment, including SLN biopsy followed by systematic pelvic lymphadenectomy, were retrospectively analyzed. A combined technique with blue dye and radiocolloid was modified in larger tumors to inject the tracer into the residual cervical stroma. RESULTS: The study included 350 patients with stages pT1a - pT2. Macrometastases, micrometastases, and isolated tumor cells were found in 10%, 8%, and 4% of cases. Bilateral detection rate was similar in subgroups with tumors<2cm, 2-3.9cm, and ≥4cm (79%, 83%, 76%) (P=0.460). There were only two cases with false-negative SLN ultrastaging for pelvic LN status among those with bilateral SLN detection. The false negative rate was very low in all three subgroups of different tumor sizes (0.9%, 0.9%, and 0.0%; P=0.999). Sensitivity reached 96% in the whole group and was high in all three groups (93%, 93%, 100%; P=0.510). CONCLUSIONS: If the tracer application technique is adjusted in larger tumors, SLN biopsy can be equally reliable in pelvic LN staging in tumors smaller and larger than 2cm. The bilateral detection rate and false negative rate did not differ in subgroups of patients with tumors<2cm, 2-3.9cm, and ≥4cm.
- MeSH
- adenokarcinom diagnóza patologie MeSH
- adenoskvamózní karcinom diagnóza patologie MeSH
- biopsie sentinelové lymfatické uzliny MeSH
- dospělí MeSH
- falešně negativní reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfadenektomie MeSH
- lymfatické metastázy MeSH
- lymfatické uzliny patologie MeSH
- mikrometastázy MeSH
- nádory děložního čípku diagnóza patologie MeSH
- pánev MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- spinocelulární karcinom diagnóza patologie MeSH
- staging nádorů MeSH
- tumor burden MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
