Neoadjuvant Radiotherapy for Malignant Lacrimal Sac Tumors

Official title

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

Overview

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.

Interventions

• 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 re
• 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.

Primary outcome measures

• overall survival at 2-year interval [Time frame: 2 years]
• overall survival at 5-year interval [Time frame: 5 years]
• overall survival at 10-year interval [Time frame: 10 years]
• disease-free survival at 2-year interval [Time frame: 2 years]
• disease-free survival at 5-year interval [Time frame: 5 years]
• disease-free survival at 10-year interval [Time frame: 10 years]
• distant metastasis-free survival at 2-year interval [Time frame: 2 years]
• distant metastasis-free survival at 5-year interval [Time frame: 5 years]
• distant metastasis-free survival at 10-year interval [Time frame: 10 years]
• locoregional control at 2-year interval [Time frame: 2 years]

Secondary outcome measures (6)

• Visual Acuity [Time frame: up to 2 years]
• Subjective Diplopia After Surgery [Time frame: up to 2 years]
• Number of Participants with Acute Radiation-Related Toxicity [Time frame: 1 month]
• Number of Participants with Chronic Radiation-Related Toxicity [Time frame: up to 2 years]
• Health-Related Quality of life [Time frame: up to 10 years]
• Ophthalmic Cancer-Related Quality of life [Time frame: up to 10 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan Eye & ENT Hospital — Shanghai

Identifiers

NCT: NCT04016675 · FD-EENT-20190701

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗