Neoadjuvant Radiotherapy for Malignant Lacrimal Sac Tumors

Long-term Outcomes of Neoadjuvant Radiotherapy Versus Adjuvant Radiotherapy for Malignant Lacrimal Sac Tumors (A Multicenter Randomized Controlled Trial)

The treatment for malignant lacrimal sac tumors is difficult and the prognosis is poor. The conventional strategy is surgical resection followed by adjuvant radiotherapy with or without concurrent chemotherapy. This approach has many drawbacks including positive surgical margins due to large tumor size, distant metastasis due to intraoperative squeeze, and implant exposure due to high doses of radiation. In previous research, the investigators innovatively adopted neoadjuvant radiotherapy (or chemoradiotherapy) and withdrew radiotherapy after surgery. Preoperative radiotherapy can effectively reduce the tumor size and encapsulate the tumor in a fibrotic cyst, and therefore enables en-bloc excision of the tumor and simultaneous orbital reconstruction. This multidisciplinary approach can reduce the risk of recurrence and metastasis, lower the dose of radiation, and avoid implant exposure after reconstruction.

In order to compare the long-term outcomes between neoadjuvant radiotherapy and conventional treatment approach, the investigators will prospectively recruit 94 patients with malignant lacrimal sac tumors and randomly assign these subjects into the study group (neoadjuvant radiotherapy, 47 cases) and the control group (conventional treatment, 47 cases). The primary outcomes include overall survival, disease-free survival, distant metastasis-free survival, and locoregional control at 2-year, 5-year and 10-year intervals. The secondary outcomes include ocular functions (visual acuity and diplopia, tear film stability and tear secretion, globe dystopia and motility, and corneal topography), acute and chronic radiation-related toxicity, cosmesis (medial canthal tendon dystopia and eyelid retraction), and assessment of quality of life.

Study Overview

• Status: Recruiting
• Conditions: Malignant Tumor of Lacrimal Drainage Structure
• Intervention / Treatment: Other: Neoadjuvant Radiotherapy/Chemoradiotherapy Followed by Surgery; Other: Surgery Followed by Adjuvant Radiotherapy/Chemoradiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 94
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan Eye & ENT Hospital
    • Contact: Jiang Qian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with suggestive symptoms, signs, imaging features and/or biopsy results for malignant lacrimal sac tumors
• Regardless of previous operations including silicone tube intubation, endoscopic dacryocystorhinostomy and incisional/needle biopsy

Exclusion Criteria:

• Recurrent tumors
• Metastatic tumors to the lacrimal sac region
• Malignant lacrimal sac tumors with previous surgical excision
• Malignant lacrimal sac tumors with local nodal or distant metastasis
• Special tumor types (e.g. lymphoma) which require non-surgical treatment
• Large tumors (invades ≥ 2/3 depth of the orbit) which require orbital exenteration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group; Neoadjuvant Radiotherapy/Chemoradiotherapy Followed by Surgery	Other: Neoadjuvant Radiotherapy/Chemoradiotherapy Followed by Surgery; After assigned into the study group, subjects will be conducted with incisional biopsy. Based on the tumor type and tumor stage, subjects will be conducted with neoadjuvant radiotherapy/chemoradiotherapy followed by radical surgery and simultaneous orbital reconstruction. After surgery, adjuvant chemotherapy will be determined based on the tumor histology, local tumor invasiveness, proximity of the surgical margins from the tumor, and pronouncement of tumor margins on permanent section tissue review.
Active Comparator: Control Group; Surgery Followed by Adjuvant Radiotherapy/Chemoradiotherapy	Other: Surgery Followed by Adjuvant Radiotherapy/Chemoradiotherapy; After assignment into the control group, subjects will receive radical surgery without simultaneous orbital reconstruction. Adjuvant radiotherapy / chemoradiotherapy will initiate within two weeks after surgery. Both the radiotherapy and chemoradiotherapy should be comparable between the study group and the control group when tumor characteristics in these two groups are identical.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival at 2-year interval	living subjects	2 years
overall survival at 5-year interval	living subjects	5 years
overall survival at 10-year interval	living subjects	10 years
disease-free survival at 2-year interval	tumor-free subjects	2 years
disease-free survival at 5-year interval	tumor-free subjects	5 years
disease-free survival at 10-year interval	tumor-free subjects	10 years
distant metastasis-free survival at 2-year interval	living subjects with no distant metastasis	2 years
distant metastasis-free survival at 5-year interval	living subjects with no distant metastasis	5 years
distant metastasis-free survival at 10-year interval	living subjects with no distant metastasis	10 years
locoregional control at 2-year interval	living subjects without local recurrence or local metastasis	2 years
locoregional control at 5-year interval	living subjects without local recurrence or local metastasis	5 years
locoregional control at 10-year interval	living subjects without local recurrence or local metastasis	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Acuity	Best-corrected visual acuity (BCVA) will be measured under standardized lighting conditions in the room, and will be converted to logarithm of the minimum angle of resolution (logMAR) values for statistical analysis.	up to 2 years
Subjective Diplopia After Surgery	Subjective diplopia will be assessed by categorizing patients according to four grades: no diplopia (absent), diplopia when the patient is tired or awakening (intermittent), diplopia at extremes of gaze (inconstant), and continuous diplopia in the primary or reading position (constant). A change of one grade is considered to be clinically relevant.	up to 2 years
Number of Participants with Acute Radiation-Related Toxicity	Acute radiation-related toxicity is defined as events occurring within 1 month after start of radiotherapy, and will be prospectively graded by the treating radiation oncologist according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5).	1 month
Number of Participants with Chronic Radiation-Related Toxicity	Chronic radiation-related toxicity is defined as events occurring or persisting > 3 months after start of radiotherapy, and will be prospectively graded by the treating radiation oncologist according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5).	up to 2 years
Health-Related Quality of life	The health-related quality of life will be assessed based on the EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Core 30 (QLQ-C30) downloaded from https://www.eortc.org. This 30-item questionnaire includes five functional scales, three symptom scales, a global health status / QoL scale, and six single items. The multi-item scales include a different set of items. Each item includes four subscales, namely "Not at all" (1 point), "A little" (2 points), "Quite a bit" (3 points) and "Very much" (4 points). The score will be recorded during each follow-up, and data will be analyzed for comparison between the study group and the control group.	up to 10 years
Ophthalmic Cancer-Related Quality of life	The ophthalmic cancer-related quality of life will be assessed based on the EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Ophthalmic Cancer Module 30 (QLQ-OPT30) downloaded from https://www.eortc.org. The QLQ-OPT30 comprises of 30 questions assessing vision impairment (9 items), functional problems due to vision impairment (8 items), eye symptoms (6 items), worry about recurrent disease (2 items), problems with appearance (1 items), problems driving (2 items), headache (1 item), problems reading (1 item). Each item includes four subscales, namely "Not at all" (1 point), "A little" (2 points), "Quite a bit" (3 points) and "Very much" (4 points). The score will be recorded during each follow-up, and data will be compared between the study group and the control group.	up to 10 years

Collaborators and Investigators

• Sponsor: Eye & ENT Hospital of Fudan University
• Collaborators: Peking University Third Hospital; Zhongshan Ophthalmic Center, Sun Yat-sen University; Tianjin Medical University Eye Hospital; Peking University Eye Center
• Investigators: Study Chair: Jiang Qian, MD, Fudan Eye & ENT Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2035

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: FD-EENT-20190701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

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