Rectal CancerLaNoReCNCT04486131
Lateral Nodal Recurrence in Rectal Cancer
An observational study of Rectal Cancer, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of the total mesorectal excision (TME) technique and neoadjuvant (chemo)radiotherapy (C))RT) to overall rates of 5-year local recurrence to 5-10%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- How many people
- 200 participants
- Where
- 1 siteNetherlands
- Study dates
- 6 Oct 2020to Oct 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with rectal cancer with one or more lateral nodes with a short-axis of ≥7mm or ≥5mm with one or more malignant features (i.e. round shape, irregular margins, heterogeneity, loss of fatty hilum).
Who may be able to join
- All patients with rectal cancer with one or more lateral nodes with a short-axis of ≥7mm or ≥5mm with one or more malignant features (i.e. round shape, irregular margins, heterogeneity, loss of fatty hilum).
Who cannot join
- Younger than 18 years old
- Pelvic irradiation in the medical history
- Previous lateral lymph node dissection related to pelvic malignancy
- Synchronous distant metastases
- Familiar adenomatous polyposis
- Synchronous colon cancer with a higher stage than rectal cancer
- Absolute contraindication for general anaesthesia
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam University Medical Centers
Amsterdam, North Holland, 1081 HV
Miranda Kusters, MD, PhD, 003120-4444444, m.kusters@amsterdamumc.nl
About this study
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of the total mesorectal excision (TME) technique and neoadjuvant (chemo)radiotherapy (C))RT) to overall rates of 5-year local recurrence to 5-10%.
However, distal rectal cancers have a tendency to spread to lateral lymph nodes and it was recently shown that patients with enlarged lateral lymph nodes of ≥7mm short-axis size have a considerable chance of a local recurrence: 15-20%. This is regardless of CRT with TME in two retrospective cohorts (Lateral Node Consortium and Snapshot Rectal Cancer 2016 study). According to the Lateral Node Consortium study, this rate was significantly reduced to <6% when performing a lateral lymph node dissection (LLND) after (C)RT + TME.
Read more
A major drawback of these recent multi-center studies is their retrospective nature. Therefore, in the Netherlands, radiologists, radiation oncologists, surgeons and pathologists have recently been educated and trained to enhance knowledge and awareness of LLNs and to implement nerve-sparing minimally invasive LLND.
The LaNoReC trial is a prospective registration study aimed at evaluating oncological outcomes after multi-disciplinary training. The main question of this study is whether, after dedicated training and the performance of LLNDs, the lateral local recurrence rate in rectal cancers with enlarged nodes (≥7mm) can be reduced to below 6%.
Read the detailed description
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of the total mesorectal excision (TME) technique. These rates have been lowered further with the use of neoadjuvant (chemo)radiotherapy ((C)RT) regimens in appropriate cases, decreasing overall rates of 5-year local recurrence to 5-10%. However, in patients with enlarged lateral lymph nodes (LLNs, ≥7mm short-axis size), recurrence rates have remained high, up to 20%. Most likely, this is caused by lymphatic spread of low rectal cancer to the lateral compartments. Western surgeons have always relied on (C)RT to sterilize the lateral compartments, containing the internal iliac and obturator lymph nodes, alleviating fears of operative morbidity and nerve function disorders associated with a lateral lymph node dissection (LLND), mainly performed in the East. Furthermore, most Western clinicians consider lateral nodal disease to represent metastatic disease, not amendable to cure.
The Lateral Node Consortium undertook a multi-centre study with 12 centres from seven countries, collecting data over a 5-year period, including all consecutive patients operated for a cT3 or T4 rectal cancer. In all patients, every series of MRIs was re-reviewed by a standardized protocol, examining lateral pelvic nodes, defining these according to size and the presence of malignant features and relating these to the development of locally recurrent disease. In the first publication of the consortium with a total of 1216 patients, it was shown that pre-treatment lateral lymph node (LLN) size of ≥7 mm, results in an unacceptably high incidence of lateral local recurrence of 20%, despite (C)RT with TME. Within the consortium, several centres performed LLND's after (C)RT, which resulted in a significantly lower rate of lateral local recurrence of 6% in nodes ≥7 mm (p = 0.042). Furthermore, LLN enlargement did not influence distant metastases rate, suggesting it is a local issue which requires to be addressed through targeted treatment in the pelvis, rather simply representing a marker of poor prognosis and distant disease.
Additionally, a second study, the Snapshot Rectal Cancer 2016 was conducted in 2020. This national retrospective cohort study included 3057 patients operated for rectal cancer in 2016 with a 4-year follow-up period. Radiologists were trained for LLN classification and measurements and re-reviewed MRIs of 882 patients with low (≤8cm from the anorectal junction), cT3/4 rectal cancer who received neoadjuvant (chemo)radiotherapy with the help of two atlases. This study found a 4-year LLR risk of 15% in presence of enlarged LLNs.
The major drawback of these multi-center studies are their retrospective nature. Radiological reporting of LLNs was low for primary MRIs, which may have influenced treatment decisions. Consequently, LLNs may have not been separately included in irradiation field. Moreover, neither study was able to investigate the effect of LLND in a trained setting. In the Netherlands, radiologists, radiation oncologists, surgeons and pathologists have recently been educated and trained to enhance knowledge and awareness of LLNs and to implement nerve-sparing minimally invasive LLND. The LaNoReC describes a prospective evaluation of oncological outcomes after multi-disciplinary training, thereby aiming for a 50% reduction in LLR rates.
- Conditions
- Rectal Cancer
- Medical subject headings
- Rectal Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Lateral local recurrence
Lateral local recurrence diagnosed during the follow up
Measured: 3 years
Secondary outcomes (6)
Disease-free survival
The measure of time after treatment during which no sign of cancer is found.
Measured: 3 years
Overall patient survival
The percentage of people who are alive 3 years after the surgery.
Measured: 3 years
Morbidity and functional outcomes assessed by LARS questions
Use of questionnaire LARS
Measured: 3 years
Quality of life as assessed by the EORTC QLQ-CR29
Quality of life as assessed by the EORTC QLQ-CR29
Measured: 3 years
Quality of life as assessed by the EQ-5D
Quality of life as assessed by the EQ-5D
Measured: 3 years
Quality of life as assessed by the QLQ-C30
Quality of life as assessed by the QLQ-C30
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2020
- Study start6 Oct 2020
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M. Kusters, Amsterdam UMC, location VUmc
- Investigators
- Miranda Kusters, MD, PhD, Principal investigator, VUMedicalCentre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04486131
- Sponsor's protocol ID
- A2021.0524.0001
- Acronym
- LaNoReC
- Status last verified
- Jan 2023
- First submitted
- 30 Jun 2020
- Last updated
- 19 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD data that underlie results in a publication can be made available upon reasonable request
Publications
Ogura A, Konishi T, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, Lee IK, Lee HX, Uehara K, Lee P, Putter H, van de Velde CJH, Beets GL, Rutten HJT, Kusters M; Lateral Node Study Consortium. Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer. J Clin Oncol. 2019 Jan 1;37(1):33-43. doi: 10.1200/JCO.18.00032. Epub 2018 Nov 7.
PubMed 30403572Ogura A, Konishi T, Beets GL, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, Lee IK, Lee HX, Uehara K, Lee P, Putter H, van de Velde CJH, Rutten HJT, Tuynman JB, Kusters M; Lateral Node Study Consortium. Lateral Nodal Features on Restaging Magnetic Resonance Imaging Associated With Lateral Local Recurrence in Low Rectal Cancer After Neoadjuvant Chemoradiotherapy or Radiotherapy. JAMA Surg. 2019 Sep 1;154(9):e192172. doi: 10.1001/jamasurg.2019.2172. Epub 2019 Sep 18.
PubMed 31268504van Geffen EGM, Sluckin TC, Hazen SJA, Horsthuis K, Intven M, van Dieren S, Beets G, Lange MM, Taggart MW, Beets-Tan RGH, Marijnen CAM, Konishi T, Tanis PJ, Kusters M; LaNoReC study group. Optimised treatment of patients with enlarged lateral lymph nodes in rectal cancer: protocol of an international, multicentre, prospective registration study after extensive multidisciplinary training (LaNoReC). BMJ Open. 2024 Oct 16;14(10):e083225. doi: 10.1136/bmjopen-2023-083225.
PubMed 39414276
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lateral Nodal Recurrence in Rectal Cancer
- ClinicalTrials.gov ID
- NCT04486131
- Acronym / sponsor ID
- LaNoReC / A2021.0524.0001
- Conditions
- Rectal Cancer
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 6 Oct 2020 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 24 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of the total mesorectal excision (TME) technique and neoadjuvant (chemo)radiotherapy (C))RT) to overall rates of 5-year local recurrence to 5-10%.
However, distal rectal cancers have a tendency to spread to lateral lymph nodes and it was recently shown that patients with enlarged lateral lymph nodes of ≥7mm short-axis size have a considerable chance of a local recurrence: 15-20%. This is regardless of CRT with TME in two retrospective cohorts (Lateral Node Consortium and Snapshot Rectal Cancer 2016 study). According to the Lateral Node Consortium study, this rate was significantly reduced to <6% when performing a lateral lymph node dissection (LLND) after (C)RT + TME.
A major drawback of these recent multi-center studies is their retrospective nature. Therefore, in the Netherlands, radiologists, radiation oncologists, surgeons and pathologists have recently been educated and trained to enhance knowledge and awareness of LLNs and to implement nerve-sparing minimally invasive LLND.
The LaNoReC trial is a prospective registration study aimed at evaluating oncological outcomes after multi-disciplinary training. The main question of this study is whether, after dedicated training and the performance of LLNDs, the lateral local recurrence rate in rectal cancers with enlarged nodes (≥7mm) can be reduced to below 6%.
Detailed description
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of the total mesorectal excision (TME) technique. These rates have been lowered further with the use of neoadjuvant (chemo)radiotherapy ((C)RT) regimens in appropriate cases, decreasing overall rates of 5-year local recurrence to 5-10%. However, in patients with enlarged lateral lymph nodes (LLNs, ≥7mm short-axis size), recurrence rates have remained high, up to 20%. Most likely, this is caused by lymphatic spread of low rectal cancer to the lateral compartments. Western surgeons have always relied on (C)RT to sterilize the lateral compartments, containing the internal iliac and obturator lymph nodes, alleviating fears of operative morbidity and nerve function disorders associated with a lateral lymph node dissection (LLND), mainly performed in the East. Furthermore, most Western clinicians consider lateral nodal disease to represent metastatic disease, not amendable to cure.
The Lateral Node Consortium undertook a multi-centre study with 12 centres from seven countries, collecting data over a 5-year period, including all consecutive patients operated for a cT3 or T4 rectal cancer. In all patients, every series of MRIs was re-reviewed by a standardized protocol, examining lateral pelvic nodes, defining these according to size and the presence of malignant features and relating these to the development of locally recurrent disease. In the first publication of the consortium with a total of 1216 patients, it was shown that pre-treatment lateral lymph node (LLN) size of ≥7 mm, results in an unacceptably high incidence of lateral local recurrence of 20%, despite (C)RT with TME. Within the consortium, several centres performed LLND's after (C)RT, which resulted in a significantly lower rate of lateral local recurrence of 6% in nodes ≥7 mm (p = 0.042). Furthermore, LLN enlargement did not influence distant metastases rate, suggesting it is a local issue which requires to be addressed through targeted treatment in the pelvis, rather simply representing a marker of poor prognosis and distant disease.
Additionally, a second study, the Snapshot Rectal Cancer 2016 was conducted in 2020. This national retrospective cohort study included 3057 patients operated for rectal cancer in 2016 with a 4-year follow-up period. Radiologists were trained for LLN classification and measurements and re-reviewed MRIs of 882 patients with low (≤8cm from the anorectal junction), cT3/4 rectal cancer who received neoadjuvant (chemo)radiotherapy with the help of two atlases. This study found a 4-year LLR risk of 15% in presence of enlarged LLNs.
The major drawback of these multi-center studies are their retrospective nature. Radiological reporting of LLNs was low for primary MRIs, which may have influenced treatment decisions. Consequently, LLNs may have not been separately included in irradiation field. Moreover, neither study was able to investigate the effect of LLND in a trained setting. In the Netherlands, radiologists, radiation oncologists, surgeons and pathologists have recently been educated and trained to enhance knowledge and awareness of LLNs and to implement nerve-sparing minimally invasive LLND. The LaNoReC describes a prospective evaluation of oncological outcomes after multi-disciplinary training, thereby aiming for a 50% reduction in LLR rates.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with rectal cancer with one or more lateral nodes with a short-axis of ≥7mm or ≥5mm with one or more malignant features (i.e. round shape, irregular margins, heterogeneity, loss of fatty hilum).
Key inclusion criteria (1 listed)
- All patients with rectal cancer with one or more lateral nodes with a short-axis of ≥7mm or ≥5mm with one or more malignant features (i.e. round shape, irregular margins, heterogeneity, loss of fatty hilum).
Key exclusion criteria (8 listed)
- Younger than 18 years old
- Pelvic irradiation in the medical history
- Previous lateral lymph node dissection related to pelvic malignancy
- Synchronous distant metastases
- Familiar adenomatous polyposis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Lateral local recurrence
Time frame: 3 years
Lateral local recurrence diagnosed during the follow up
6 secondary outcomes
Disease-free survival
Time frame: 3 years
Overall patient survival
Time frame: 3 years
Morbidity and functional outcomes assessed by LARS questions
Time frame: 3 years
Quality of life as assessed by the EORTC QLQ-CR29
Time frame: 3 years
Quality of life as assessed by the EQ-5D
Time frame: 3 years
Quality of life as assessed by the QLQ-C30
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2023.
- Results publication: PubMed 30403572Ogura A, Konishi T, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, Lee IK, Lee HX, Uehara K, Lee P, Putter H, van de Velde CJH, Beets GL, Rutten HJT, Kusters M; Lateral Node Study Consortium. Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer. J Clin Oncol. 2019 Jan 1;37(1):33-43. doi: 10.1200/JCO.18.00032. Epub 2018 Nov 7.
- Results publication: PubMed 31268504Ogura A, Konishi T, Beets GL, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, Lee IK, Lee HX, Uehara K, Lee P, Putter H, van de Velde CJH, Rutten HJT, Tuynman JB, Kusters M; Lateral Node Study Consortium. Lateral Nodal Features on Restaging Magnetic Resonance Imaging Associated With Lateral Local Recurrence in Low Rectal Cancer After Neoadjuvant Chemoradiotherapy or Radiotherapy. JAMA Surg. 2019 Sep 1;154(9):e192172. doi: 10.1001/jamasurg.2019.2172. Epub 2019 Sep 18.
- Derived from this study: PubMed 39414276van Geffen EGM, Sluckin TC, Hazen SJA, Horsthuis K, Intven M, van Dieren S, Beets G, Lange MM, Taggart MW, Beets-Tan RGH, Marijnen CAM, Konishi T, Tanis PJ, Kusters M; LaNoReC study group. Optimised treatment of patients with enlarged lateral lymph nodes in rectal cancer: protocol of an international, multicentre, prospective registration study after extensive multidisciplinary training (LaNoReC). BMJ Open. 2024 Oct 16;14(10):e083225. doi: 10.1136/bmjopen-2023-083225.
- Individual participant dataSharing planned: Yes. IPD data that underlie results in a publication can be made available upon reasonable request
Related trials for Rectal Cancer
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
A Study of MGC030 in Participants With Advanced Solid Tumors
Urothelial Cancer, GastroEsophageal Cancer
Not yet recruitingPhase 2
Exploratory Study of Short-Course Radiotherapy Followed by Adebrelimab Combined With Chemotherapy for Organ Preservation in Locally Advanced Rectal Cancer
Locally Advanced Resectable Rectal Cancer
RecruitingObservational study
ABCSG R07 Rectal Cancer Registry
Rectal Cancer, Adenocarcinoma of Rectum
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Miranda Kusters, MD, PhD principal investigator
VUMedicalCentre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rectal Cancer, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Miranda Kusters, MD, PhD (0031204444444, m.kusters@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lateral local recurrence (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04486131, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2023.