Management of LLN Metastasis in Locally Advanced Rectal Cancer: A Prospective Radiation Dose Escalation Study

Management of Clinically Involved Lateral Lymph Node Metastasis in Locally Advanced Rectal Cancer: A Prospective Radiation Dose Escalation Study

In this study, locally advanced rectal cancer (LARC) patients with lateral lymph node (LLN) metastasis would be enrolled. The LLNs with short axis (SA) ≥ 5 mm are considered metastatic.The safety of neoadjuvant chemoradiotherapy(nCRT) with a booster dose to 58Gy had been initially demonstrated in our previous research. The effective and safety of dose escalation of LLN in LARC patients, will be further verified in this prospective, clinical study.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: escalation dose of LLNs

Detailed Description

This is a prospective, observational clinical study for validation the efficiency and safety of the dose escalation of LLN. Patients who have been pathologically diagnosed as rectal adenocarcinoma and defined as clinical T1-4N1-2M0 without distant metastasis will be enrolled from the Sixth Affiliated Hospital of Sun Yat-sen University. Patients should have at least one LLN metastasis defined on primary MRI, and the data of primary pelvic MRI will be performed within two weeks before the beginning of enrollment. All patients should follow a standard treatment protocol, including concurrent neoadjuvant chemoradiotherapy (nCRT) with a dose boost of LLNs to 58Gy, TME surgery with or without LLND ( lateral lymph node dissection) and adjuvant chemotherapy. The regimen of chemotherapy and the way of operation should be depended on the MDT(multiply discipline treatment) decision. The restaged MRI scan would be performed 6-12 weeks after the last fraction of radiotherapy. The LLN response rate ( short axis < 5mm ) would be evaluated. This study is aimed to apply a new way to control LLN metastasis.

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaolin Pang, MD; Phone Number: +86 13928734386; Email: pangxl5@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • The sixth affiliated hospital of Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• informed consent was signed ;
• Age 18-75;
• Pathologically confirmed rectal adenocarcinoma, colonoscopy,MRI, CT and other examinations confirmed that the tumor was located under peritoneal reflexion,
• clinical staging was T1-4N1-2M0, pelvic MRI evaluation showed at least one lateral lymph node with short diameter ≥5 mm;
• Pelvic MRI was evaluated no more than 14 days before enrollment;
• ECOG 0-2 points;
• No prior history of other malignant tumors, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix.

Exclusion Criteria:

• Previous radiotherapy or surgical treatment for colorectal cancer (except biopsy for pathology);
• Whole body CT, MR or PET-CT (including at least chest, whole abdomen, and pelvis) confirmed distant metastasis (M1);
• Previous or coexisting active malignancies (other than malignant neoplasms that have received curable treatment and have not been present for more than 3 years or carcinoma in situ that can be cured by adequate treatment);
• Receiving major operations such as laparotomy, thoracotomy, laparoscopic resection of organs or serious external injuries within the previous 4 weeks;
• Active coronary artery disease, severe/unstable angina pectoris or newly diagnosed angina or myocardial infarction within the 12 months prior to study participation;
• Patients who have experienced thrombosis or embolism within the past 6 months have received radiotherapy or surgical treatment for rectal cancer (except biopsy for pathology)
• New York Heart Society (NYHA) Grade II or higher congestive heart failure;
• The presence of CTCAE grade 2 or above toxicity (except anemia, alopecia, and skin pigmentation) due to any previous treatment that has not resolved;
• Pregnant or lactating women;
• Accompany with any medical condition that would affect patient safety and study compliance;
• Patients determined by the investigator to be unsuitable for participation in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: escalation; The gross tumor volume (GTV) was defined as gross disease determined on MRI scans. The clinical target volume (CTV) was defined as the GTV plus areas considered at significant risk of harboring microscopic area. The lymph nodes (SA ≥ 5 mm) existed at the internal iliac and obturator would be delineated, named as GTVnd, and received a radiation dose boost. The planning target volume (PTV) was generated by adding an 8-mm margin around the GTV, GTVnd, and CTV in all directions. Doses of 58 Gy, 50 Gy, and 45 Gy were delivered to PTV-GTVnd, PTV-GTV, and PTV-CTV at 25 fractions, respectively. The dose of the normal organs at risk was constrained to the following criteria: bowel bag, V50 ≤ 5%; bladder, V50 ≤ 50%; femoral heads, V50 ≤ 5% .

Radiation: escalation dose of LLNs; The lymph nodes (SA ≥ 5 mm) existed at the internal iliac and obturator would be delineated, named as GTVnd, and received a radiation dose boost of 58Gy.; Other Names: escalation group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the responsive rate of dose escalation of LLN	the LLN responsive rate (short diameter < 5mm) of neoadjuvant chemoradiotherapy combined with dose escalation of LLN in the treatment of middle and low locally advanced rectal cancer	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prognosis outcome-3-year Local Recurrence	The 3-year Local Recurrence of LARC patients underwent neoadjuvant chemoradiotherapy combined with dose escalation of LLN	3 years
prognosis outcome-3-year Lateral Local Recurrence	The 3-year Lateral Local Recurrence of LARC patients underwent neoadjuvant chemoradiotherapy combined with dose escalation of LLN	3 years

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Investigators: Study Chair: Xiangbo Wan, MD, Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2021
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): August 28, 2024

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: August 4, 2021
• First Posted (Actual): August 5, 2021

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: Dose-esclation-LLN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No